volume 15, issue 4 - winter 2016-17

PluggingProfit Leaks

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ION Solutions Educational Programs

2017 Meeting Schedule

Meeting Date Meeting Name Location Venue

March 10-12 Oral Therapies Fort Worth, TX Omni

September 8-10National Healthcare Practitioners

Charlotte, NC Westin Charlotte

November 3-5 ION National Baltimore, MD Hilton

All ION Solutions meeting materials are archived on iononline.com. Visit the website to view slides and videos from past meetings.

Serious Adverse ReactionsPlease refer to the full Prescribing Information for important dose management information specific to adverse reactions.• Immune-related pneumonitis. Immune-mediated pneumonitis or interstitial

lung disease have occurred. Fatal cases have been observed in patients with urothelial carcinoma (UC) and non-small cell lung cancer (NSCLC). Permanently discontinue TECENTRIQ for Grade 3 or 4 pneumonitis

• Immune-related hepatitis. Immune-mediated hepatitis and liver test abnormalities, including a fatal case of hepatitis in a patient with UC, have occurred. Permanently discontinue TECENTRIQ for Grade 3 or 4 immune-mediated hepatitis

• Immune-related colitis. Immune-mediated colitis or diarrhea, including a fatal case of diarrhea-associated renal failure in a patient with UC, occurred. Permanently discontinue TECENTRIQ for Grade 4 diarrhea or colitis

• Immune-related endocrinopathies. Immune-related thyroid disorders, adrenal insufficiency, hypophysitis, and type 1 diabetes mellitus, including diabetic ketoacidosis, have occurred. Permanently discontinue TECENTRIQ for Grade 4 hypophysitis

• Other immune-related adverse reactions. Meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred. Permanently discontinue TECENTRIQ for any grade of meningitis or encephalitis, or any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome. Permanently discontinue TECENTRIQ for Grade 4 or any grade of recurrent pancreatitis

• Infection. Severe infections, such as sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage, have occurred. Fatal cases have been observed in patients with UC and NSCLC

• Infusion-related reactions. Severe infusion reactions occurred. Permanently discontinue TECENTRIQ in patients with Grade 3 or 4 infusion reactions

• Embryo-fetal toxicity. TECENTRIQ can cause fetal harm in pregnant women. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose

• Advise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose

Most Common Adverse ReactionsThe most common adverse reactions (rate ≥20%) in UC included fatigue (52%), decreased appetite (26%), nausea (25%), urinary tract infection (22%), pyrexia (21%), and constipation (21%).

The most common adverse reactions in NSCLC (rate ≥20%) included fatigue (46%), decreased appetite (35%), dyspnea (32%), cough (30%), nausea (22%), musculoskeletal pain (22%), and constipation (20%).

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see Brief Summary of Prescribing Information on adjacent pages.

© 2016 Genentech USA, Inc. All rights reserved. PDL/072716/0182

TECENTRIQ is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:• Have disease progression during or following platinum-containing chemotherapy • Have disease progression within 12 months of neoadjuvant or adjuvant

treatment with platinum-containing chemotherapy

TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

FOR PREVIOUSLY TREATED LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA

FOR PREVIOUSLY TREATED METASTATIC NON-SMALL CELL LUNG CANCER

NOW APPROVED FOR 2 TUMOR TYPES

THE FIRST AND ONLY FDA-APPROVED ANTI-PDL1 CANCER IMMUNOTHERAPY

TECENTRIQ®

Learn more at TECENTRIQ.com/learn

ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; PD-L1=programmed death-ligand 1.

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7” x 10”7.75” x 10.5”None

1/0 B/W

Colors Black

FontsHelvetica Neue LT Std (77 Bold Condensed, 57 Condensed, 57 Condensed Oblique, 77 Bold Con-densed Oblique, 107 Extra Black Condensed)

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Gene_Logo_K_T.ai (42.87%)

Notes Brief Summary - Lung. A size

TECENTRIQ N = 310

Adverse Reaction All Grades (%) Grades 3–4 (%)General Disorders and AdministrationFatigue 52 6Pyrexia 21 1Peripheral edema 18 1Infections and InfestationsUrinary tract infection 22 9Metabolism and Nutrition DisordersDecreased appetite 26 1Musculoskeletal and Connective Tissue DisordersBack/Neck pain 15 2Arthralgia 14 1Renal and urinary disordersHematuria 14 3Respiratory, Thoracic, and Mediastinal DisordersDyspnea 16 4Cough 14 0.3Skin and Subcutaneous Tissue DisordersRash 15 0.3Pruritus 13 0.3

Table 2: Grade 3–4 Laboratory Abnormalities in Patients with Urothelial Carcinoma in Study 1 in ≥ 1% of Patients

Laboratory Test Grades 3–4 (%)

Lymphopenia 10

Hyponatremia 10

Anemia 8

Hyperglycemia 5

Increased Alkaline phosphatase 4

Increased Creatinine 3

Increased ALT 2

Increased AST 2

Hypoalbuminemia 1

NSCLCThe safety of TECENTRIQ was evaluated in Study 3, a multi-center, international, randomized, open-label trial in patients with metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression [see Clinical Studies (14.2)].  Patients received 1200 mg of TECENTRIQ (n=142) administered intravenously every 3 weeks until unacceptable toxicity or either radiographic or clinical progression or docetaxel (n=135) administered intravenously at 75 mg/m2 every 3 weeks until unacceptable toxicity or disease progression. The median duration of exposure was 3.7 months (range: 0–19 months) in TECENTRIQ-treated patients and 2.1 months (range: 0–17 months) in docetaxel-treated patients.The most common adverse reactions (≥ 20%) in patients receiving TECENTRIQ were fatigue (46%), decreased appetite (35%), dyspnea (32%), cough (30%), nausea (22%), musculoskeletal pain (22%), and constipation (20%). The most common Grade 3-4 adverse reactions (≥2%) were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia.Nine patients (6.3%) who were treated with TECENTRIQ experienced either pulmonary embolism (2), pneumonia (2), pneumothorax, ulcer hemorrhage, cachexia secondary to dysphagia, myocardial infarction, or large intestinal perforation which led to death. TECENTRIQ was discontinued due to adverse reactions in 4% (6/142) of patients. Adverse reactions leading to interruption of TECENTRIQ occurred in 24% of patients; the most common (>1%) were pneumonia, liver function test abnormality, upper respiratory tract infection, pneumonitis, acute kidney injury, hypoxia, hypothyroidism, dyspnea, anemia, and fatigue. Serious adverse reactions occurred in 37% of patients. The most frequent serious adverse reactions (> 2%) were pneumonia, dyspnea, pleural effusion, pyrexia, and venous thromboembolism.Table 3 summarizes adverse reactions that occurred in at least 10% of TECENTRIQ-treated patients and at a higher incidence than in the docetaxel arm. Table 4 summarizes selected laboratory abnormalities worsening from baseline that occurred in ≥10% of TECENTRIQ-treated patients and at a higher incidence than in the docetaxel arm.

Table 3: Adverse Reactions Occurring in ≥10% of TECENTRIQ-Treated Patients with NSCLC and at a Higher Incidence than in the Docetaxel Arm (Between Arm Difference of ≥5% [All Grades] or ≥2% [Grades 3–4]) (Study 3)

TECENTRIQ(n=142)

Docetaxel(n=135)

Adverse Reaction All grades Grade 3–4 All grades Grade 3–4Percentage (%) of Patients

General Disorders and Administration Site ConditionsPyrexia 18 0 13 0

Infections and infestationsPneumonia 18 6 4 2

Metabolism and nutrition disorders Decreased appetite 35 1 22 0

Musculoskeletal and connective tissue disordersArthralgia 16 2 9 2

Back Pain 14 1 9 1

Psychiatric Disorders Insomnia 14 0 8 2

Respiratory, thoracic and mediastinal disorders Dyspnea 32 7 24 2

Cough 30 1 25 0

Table 4: Selected Laboratory Abnormalities Worsening from Baseline Occurring in ≥10% of TECENTRIQ-Treated Patients with NSCLC and at a Higher Incidence than in the Docetaxel Arm (Between Arm Difference of ≥5% [All Grades] or ≥2% [Grades 3–4]) (Study 3)

Percentage of Patients with WorseningLaboratory Test from Baseline

TECENTRIQ Docetaxel

Test All grades (%) Grade 3–4 (%) All grades (%) Grade 3–4 (%)

Hyponatremia 48 13 28 8

Hypoalbuminemia 48 5 49 1

Alkaline Phosphatase increased 42 2 24 1

Aspartate aminotransferase increased 33 2 15 0

Alanine aminotransferase increased 31 2 9 1

Creatinine increased 19 1 14 2

Hypokalemia 18 2 11 4

Hypercalcemia 13 0 5 0

Total Bilirubin increased 11 0 5 1

6.2 ImmunogenicityAs with all therapeutic proteins, there is a potential for immunogenicity. Among 275  patients in Study  1, 114 patients (41.5%) tested positive for treatment-emergent (treatment-induced or treatment-enhanced) anti-therapeutic antibodies (ATA) at one or more post-dose time points. Among 135 patients in Study 3, 73 patients (54.1%) tested positive for treatment-emergent (treatment-induced or treatment-enhanced) anti-therapeutic antibodies (ATA) at one or more post-dose time points. In Study 1 and Study 3, the presence of ATAs did not appear to have a clinically significant impact on pharmacokinetics, safety or efficacy.Immunogenicity assay results are highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of incidence of ATAs to TECENTRIQ with the incidence of antibodies to other products may be misleading.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyRisk SummaryBased on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of TECENTRIQ in pregnant women. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus resulting in fetal death [see Data]. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.DataAnimal DataAnimal reproduction studies have not been conducted with TECENTRIQ to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects on reproduction demonstrated that a central function of the PD-L1/PD-1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to a fetus. Blockage of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to result in an increase in fetal loss; therefore, potential risks of administering TECENTRIQ during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-L1/PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response. 8.2 LactationRisk SummaryThere is no information regarding the presence of atezolizumab in human milk, the effects on the breastfed infant, or the effects on milk production. As human IgG is excreted in human milk, the potential for absorption and harm to the infant is unknown. Because of the potential for serious adverse reactions in breastfed infants from TECENTRIQ, advise a lactating woman not to breastfeed during treatment and for at least 5 months after the last dose. 8.3 Females and Males of Reproductive PotentialContraceptionFemalesBased on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ and for at least 5 months following the last dose.InfertilityFemalesBased on animal studies, TECENTRIQ may impair fertility in females of reproductive potential while receiving treatment [see Nonclinical Toxicology (13.1)].8.4 Pediatric UseThe safety and effectiveness of TECENTRIQ have not been established in pediatric patients.8.5 Geriatric UseOf the 310 patients with urothelial carcinoma treated with TECENTRIQ in Study 1, 59% were 65 years or older. Of the 142 patients with NSCLC treated with TECENTRIQ in Study 3, 39% were 65 years or older. No overall differences in safety or efficacy were observed between patients ≥ 65 years of age and younger patients.8.6 Renal ImpairmentBased on a population pharmacokinetic analysis, no dose adjustment of TECENTRIQ is recommended for patients with renal impairment [see Clinical Pharmacology (12.3)].8.7 Hepatic ImpairmentBased on a population pharmacokinetic analysis, no dose adjustment of TECENTRIQ is recommended for patients with mild hepatic impairment. TECENTRIQ has not been studied in patients with moderate or severe hepatic impairment [see Clinical Pharmacology (12.3)].10 OVERDOSAGEThere is no information on overdose with TECENTRIQ.17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Medication Guide).Inform patients of the risk of immune-related adverse reactions that may require corticosteroid treatment and interruption or discontinuation of TECENTRIQ, including: • Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening

cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1)]. • Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea

or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding [see Warnings and Precautions (5.2)].

• Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.3)].

• Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypophysitis, hyperthyroidism, hypothyroidism, adrenal insufficiency, or type 1 diabetes mellitus, including diabetic ketoacidosis [see Warnings and Precautions (5.4)]

• Meningoencephalitis, myasthenic syndrome/myasthenia gravis, and Guillain-Barré syndrome: Advise patients to contact their healthcare provider immediately for signs or symptoms of meningitis, myasthenic syndrome/myasthenia gravis, or Guillain-Barré syndrome [see Warnings and Precautions (5.5)].

• Ocular Inflammatory Toxicity: Advise patients to contact their healthcare provider immediately for signs or symptoms of ocular inflammatory toxicity [see Warnings and Precautions (5.5)].

• Pancreatitis: Advise patients to contact their healthcare provider immediately for signs and symptoms of pancreatitis [see Warnings and Precautions (5.5)].

• Infection: Advise patients to contact their healthcare provider immediately for signs or symptoms of infection [see Warnings and Precautions (5.6)].

• Infusion-Related Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.7)].

• Rash: Advise patients to contact their healthcare provider immediately for signs or symptoms of rash [see Dosage and Administration (2.2)].

Embryo-Fetal ToxicityAdvise female patients that TECENTRIQ can cause fetal harm. Instruct females of reproductive potential to use effective contraception during treatment and for at least 5 months after the last dose of TECENTRIQ [see Use in Specific Populations (8.1, 8.3)].LactationAdvise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose [see Use in Specific Populations (8.2)].

TECENTRIQ® (atezolizumab)

Manufactured by: PDL/080916/0193Genentech, Inc. Initial U.S. Approval: May 2016A Member of the Roche Group Code Revision Date: October 20161 DNA Way TECENTRIQ is a registered trademark of Genentech, Inc.South San Francisco, CA 94080-4990 © 2016 Genentech, Inc.

U.S. License No. 1048

S:7”S:10”

T:7.75”T:10.5”

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PDL1-64934_M7_NSCLC-BS_Asze.indd10-21-2016 12:12 PM Taylor Raczkowski / Paul LaRocca

Client CodeClient

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PDL/080916/0193Genentech/PDL1

7” x 10”7.75” x 10.5”None

1/0 B/W

Colors Black

FontsHelvetica Neue LT Std (77 Bold Condensed, 57 Condensed, 57 Condensed Oblique, 77 Bold Con-densed Oblique, 107 Extra Black Condensed)

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Notes Brief Summary - Lung. A size

TECENTRIQ® [atezolizumab]Initial U.S. Approval: 2016This is a brief summary of information about TECENTRIQ. Before prescribing, please see full Prescribing Information.1 INDICATIONS AND USAGE1.1 Locally Advanced or Metastatic Urothelial CarcinomaTECENTRIQ (atezolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: • Have disease progression during or following platinum-containing chemotherapy • Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing

chemotherapyThis indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies (14.1)].1.2 Metastatic Non-Small Cell Lung CancerTECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ [see Clinical Studies (14.2)].4 CONTRAINDICATIONSNone.5 WARNINGS AND PRECAUTIONS 5.1 Immune-Related Pneumonitis Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer steroids at a dose of 1 to 2 mg/kg/day prednisone equivalents for Grade 2 or greater pneumonitis, followed by corticosteroid taper. Withhold TECENTRIQ until resolution for Grade 2 pneumonitis. Permanently discontinue TECENTRIQ for Grade 3 or 4 pneumonitis [see Dosage and Administration (2.2)]. Across clinical trials, 2.6% (51/1978) of patients developed pneumonitis. Fatal pneumonitis occurred in two patients.Urothelial CarcinomaIn 523 patients with urothelial carcinoma who received TECENTRIQ, pneumonitis occurred in six (1.1%) patients. Of these patients, there was one patient with fatal pneumonitis, one patient with Grade 3, three patients with Grade 2, and one patient with Grade 1 pneumonitis. TECENTRIQ was held in all cases and five patients were treated with corticosteroids. Pneumonitis resolved in three patients. The median time to onset was 2.6 months (range: 15 days to 4.2 months). The median duration was 15 days (range: 6 days to 3.1+ months).NSCLCIn 1027 patients with NSCLC who received TECENTRIQ, pneumonitis occurred in 38 (3.7%) patients. Of these patients, there was one patient with fatal pneumonitis, two patients with Grade 4, thirteen patients with Grade 3, eleven patients with Grade 2, and eleven patients with Grade 1 pneumonitis. TECENTRIQ was held in 24 patients and 21 patients were treated with corticosteroids. Pneumonitis resolved in 26 of the 38 patients. The median time to onset was 3.3 months (range: 3 days to 18.7 months). The median duration was 1.4 months (range: 0 days to 12.6+ months).5.2 Immune-Related Hepatitis Immune-mediated hepatitis, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ treatment. Liver test abnormalities occurred in patients who received TECENTRIQ. Monitor patients for signs and symptoms of hepatitis. Monitor AST, ALT, and bilirubin prior to and periodically during treatment with TECENTRIQ. Administer corticosteroids at a dose of 1–2 mg/kg/day prednisone equivalents for Grade 2 or greater transaminase elevations, with or without concomitant elevation in total bilirubin, followed by corticosteroid taper. Withhold TECENTRIQ for Grade 2 and permanently discontinue TECENTRIQ for Grade 3 or 4 immune-mediated hepatitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)].Across clinical trials (n=1978), Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.3%), and total bilirubin (1.6%).Urothelial CarcinomaIn patients with urothelial carcinoma (n=523), Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.5%), and total bilirubin (2.1%). Immune-mediated hepatitis occurred in 1.3% of patients. Of these cases, one patient died from hepatitis, five patients had Grade 3, and one patient had Grade 2 hepatitis. The median time to onset was 1.1 months (range: 0.4 to 7.7 months). TECENTRIQ was temporarily interrupted in four patients; none of these patients developed recurrence of hepatitis after resuming TECENTRIQ. NSCLCIn patients with NSCLC, Grade 3 or 4 elevation occurred in ALT (1.4%), AST (1.3%), and total bilirubin (0.6%). Immune-mediated hepatitis occurred in 0.9% (9/1027) of patients. Of these nine patients, one patient had Grade 4, four patients had Grade 3, three patients had Grade 2, and one patient had Grade 1 immune-mediated hepatitis. The median time to onset was 28 days (range: 15 days to 4.2 months). TECENTRIQ was temporarily interrupted in seven patients; none of these patients developed recurrence of hepatitis after resuming TECENTRIQ.5.3 Immune-Related ColitisImmune-mediated colitis or diarrhea, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ. Monitor patients for signs and symptoms of diarrhea or colitis. Withhold treatment with TECENTRIQ for Grade 2 diarrhea or colitis. If symptoms persist for longer than 5 days or recur, administer 1–2 mg/kg prednisone or equivalent per day. Withhold treatment with TECENTRIQ for Grade 3 diarrhea or colitis. Treat with IV methylprednisolone 1–2 mg/kg per day and convert to oral steroids once the patient has improved. For both Grade 2 and Grade 3 diarrhea or colitis, when symptoms improve to Grade 0 or Grade 1, taper steroids over ≥ 1 month. Resume treatment with TECENTRIQ if the event improves to Grade 0 or 1 within 12 weeks and corticosteroids have been reduced to the equivalent of ≤ 10 mg oral prednisone per day. Permanently discontinue TECENTRIQ for Grade 4 diarrhea or colitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Across clinical trials, colitis or diarrhea occurred in 19.7% (389/1978) of all patients. Urothelial CarcinomaIn 523 patients with urothelial carcinoma who received TECENTRIQ, colitis or diarrhea occurred in 98 (18.7%) patients. Ten patients (1.9%) developed Grade 3 or 4 diarrhea. Four patients (0.8%) had immune-mediated colitis or diarrhea with a median time to onset of 1.7 months (range: 1.1 to 3.1 months). Immune-mediated colitis resolved with corticosteroid administration in three of these patients, while the other patient died without resolution of colitis in the setting of diarrhea-associated renal failure.NSCLCIn 1027 patients with NSCLC who received TECENTRIQ, colitis or diarrhea occurred in 198 (19.3%) patients. Twelve patients (1.2%) developed Grade 3 colitis or diarrhea. Five patients (0.5%) had immune-mediated colitis or diarrhea with a median time to onset of 21 days (range: 12 days to 3.4 months). Of these patients, one had Grade 3, two had Grade 2, and two had Grade 1 immune-mediated colitis or diarrhea. Immune-mediated colitis or diarrhea resolved with corticosteroid administration in four of these patients, while the fifth patient died due to disease progression prior to resolution of colitis. 5.4 Immune-Related Endocrinopathies Immune-related thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, have occurred in patients receiving TECENTRIQ. Monitor patients for clinical signs and symptoms of endocrinopathies.HypophysitisHypophysitis occurred in 0.2% (1/523) of patients with urothelial cancer receiving TECENTRIQ. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids and hormone replacement as clinically indicated. Withhold TECENTRIQ for Grade 2 or Grade 3 and permanently discontinue for Grade 4 hypophysitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Thyroid DisordersThyroid function was assessed routinely only at baseline and the end of the study. Monitor thyroid function prior to and periodically during treatment with TECENTRIQ. Asymptomatic patients with abnormal thyroid function tests can receive TECENTRIQ. For symptomatic hypothyroidism, withhold TECENTRIQ and initiate thyroid hormone replacement as needed. Manage isolated hypothyroidism with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold TECENTRIQ and initiate an anti-thyroid drug as needed. Resume treatment with TECENTRIQ when symptoms of hypothyroidism or hyperthyroidism are controlled and thyroid function is improving [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Across clinical trials, hypothyroidism and hyperthyroidism occurred in 3.9% (77/1978) and 1.0% (20/1978) of patients, respectively.Urothelial CarcinomaIn 523 patients with urothelial carcinoma who received TECENTRIQ, hypothyroidism occurred in 2.5% (13/523). One patient had Grade 3 and twelve patients had Grade 1–2 hypothyroidism. The median time to first onset was 5.4 months (range: 21 days to 11.3 months). Thyroid stimulating hormone (TSH) was elevated and above the patient’s baseline in 16% (21/131) of patients with a follow-up measurement.Hyperthyroidism occurred in 0.6% (3/523) of patients with urothelial carcinoma. Of the three urothelial carcinoma patients, one patient had Grade 2 and two patients had Grade 1 hyperthyroidism. The median time to onset was 3.2 months (range: 1.4 to 5.8 months). TSH was decreased and below the patient’s baseline in 3.8% (5/131) of patients with a follow-up measurement.NSCLCIn 1027 patients with NSCLC who received TECENTRIQ, hypothyroidism occurred in 4.2% (43/1027). Three patients had Grade 3 and forty patients had Grade 1–2 hypothyroidism. The median time to onset was 4.8 months (range 15 days to 31 months.) TSH was elevated and above the patient’s baseline in 17% (54/315) of patients with follow-up measurement.

Hyperthyroidism occurred in 1.1% (11/1027) of patients with NSCLC. Eight patients had Grade 2 and three patients had Grade 1 hyperthyroidism. The median time to onset was 4.9 months (range: 21 days to 31 months). TSH was decreased and below the patient’s baseline in 7.6% (24/315) of patients with a follow-up measurement.Adrenal InsufficiencyAdrenal insufficiency occurred in 0.4% (7/1978) of patients across clinical trials, including two patients with Grade 3, four patients with Grade 2, and one patient with Grade 1. Adrenal insufficiency resolved in two patients. For symptomatic adrenal insufficiency, withhold TECENTRIQ and administer methylprednisolone 1–2 mg/kg per day IV followed by oral prednisone 1–2 mg/kg per day or equivalent once symptoms improve. Start steroid taper when symptoms improve to ≤ Grade 1 and taper steroids over ≥ 1 month. Resume treatment with TECENTRIQ if the event improves to ≤ Grade 1 within 12 weeks and corticosteroids have been reduced to the equivalent of ≤ 10 mg oral prednisone per day and the patient is stable on replacement therapy, if required [see Dosage and Administration (2.2) and Adverse Reactions (6.1)].Diabetes MellitusNew onset diabetes with ketoacidosis has occurred in patients receiving TECENTRIQ. Diabetes mellitus without an alternative etiology occurred in one (0.2%) patient with urothelial carcinoma and three (0.3%) patients with NSCLC.Initiate treatment with insulin for type 1 diabetes mellitus. For ≥ Grade 3 hyperglycemia (fasting glucose >250–500 mg/dL), withhold TECENTRIQ. Resume treatment with TECENTRIQ when metabolic control is achieved on insulin replacement therapy [see Dosage and Administration (2.2) and Adverse Reactions (6.1)].5.5 Other Immune-Related Adverse Reactions Other immune-related adverse reactions including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤ 1.0% of patients treated with TECENTRIQ. Meningitis / EncephalitisMonitor patients for clinical signs and symptoms of meningitis or encephalitis. Permanently discontinue TECENTRIQ for any grade of meningitis or encephalitis. Treat with IV steroids (1–2 mg/kg/day methylprednisolone or equivalent) and convert to oral steroids (prednisone 60 mg/day or equivalent) once the patient has improved. When symptoms improve to ≤ Grade 1, taper steroids over ≥ 1 month [see Dosage and Administration (2.2) and Adverse Reactions (6.1)].Motor and Sensory NeuropathyMonitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue TECENTRIQ for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome. Institute medical intervention as appropriate. Consider initiation of systemic corticosteroids at a dose of 1–2 mg/kg/day prednisone [see Dosage and Administration (2.2) and Adverse Reactions (6.1)].PancreatitisSymptomatic pancreatitis without an alternative etiology occurred in 0.1% (2/1978) of patients across clinical trials. Monitor patients for signs and symptoms of acute pancreatitis. Withhold TECENTRIQ for ≥ Grade 3 serum amylase or lipase levels (> 2.0 ULN), or Grade 2 or 3 pancreatitis. Treat with 1–2 mg/kg IV methylprednisolone or equivalent per day. Once symptoms improve, follow with 1–2 mg/kg of oral prednisone or equivalent per day. Resume treatment with TECENTRIQ when serum amylase and lipase levels improve to ≤ Grade 1 within 12 weeks or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to ≤ 10 mg oral prednisone or equivalent per day. Permanently discontinue TECENTRIQ for Grade 4 or any grade of recurrent pancreatitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. 5.6 InfectionSevere infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage occurred in patients receiving TECENTRIQ. Monitor patients for signs and symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Withhold TECENTRIQ for ≥ Grade 3 infection [see Dosage and Administration (2.2) and Adverse Reactions (6.1)].Across clinical trials, infections occurred in 38.4% (759/1978) of patients. Urothelial CarcinomaIn 523 patients with urothelial carcinoma who received TECENTRIQ, infection occurred in 197 (37.7%) patients. Grade 3 or 4 infection occurred in sixty (11.5%) patients, while three patients died due to infections. Urinary tract infections were the most common cause of Grade 3 or higher infection, occurring in 37 (7.1%) patients.NSCLCIn Study 3, a randomized trial in patients with NSCLC, infections were more common in patients treated with TECENTRIQ (43%) compared with those treated with docetaxel (34%). Grade 3 or 4 infections occurred in 9.2% of patients treated with TECENTRIQ compared with 2.2% in patients treated with docetaxel. Two patients (1.4%) treated with TECENTRIQ and three patients (2.2%) treated with docetaxel died due to infection. Pneumonia was the most common cause of Grade 3 or higher infection, occurring in 7.7% of patients treated with TECENTRIQ.5.7 Infusion-Related ReactionsSevere infusion reactions have occurred in patients in clinical trials of TECENTRIQ. Infusion-related reactions occurred in 1.3% (25/1978) of patients across clinical trials, 1.7% (9/523) of patients with urothelial carcinoma, and 1.6% (16/1027) of patients with NSCLC. Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions. Permanently discontinue TECENTRIQ in patients with Grade 3 or 4 infusion reactions [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. 5.8 Embryo-Fetal ToxicityBased on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus resulting in fetal death. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose [see Use in Specific Populations (8.1, 8.3)].6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: • Immune-Related Pneumonitis [see Warnings and Precautions (5.1)] • Immune-Related Hepatitis [see Warnings and Precautions (5.2)] • Immune-Related Colitis [see Warnings and Precautions (5.3)] • Immune-Related Endocrinopathies [see Warnings and Precautions (5.4)] • Other Immune-Related Adverse Reactions [see Warnings and Precautions (5.5)] • Infection [see Warnings and Precautions (5.6)] • Infusion-Related Reactions [see Warnings and Precautions (5.7)]6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.Urothelial CarcinomaThe data described in Table  1 reflects exposure to TECENTRIQ in Cohort 2 of Study 1. This cohort enrolled 310  patients in a single arm trial with locally advanced or metastatic urothelial carcinoma who had disease progression during or following at least one platinum-containing chemotherapy regimen or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen [see Clinical Studies (14.1)]. Patients received 1200 mg of TECENTRIQ intravenously every 3 weeks until unacceptable toxicity or either radiographic or clinical progression. The median duration of exposure was 12.3 weeks (range: 0.1, 46 weeks). The most common adverse reactions (≥ 20%) were fatigue (52%), decreased appetite (26%), nausea (25%), urinary tract infection (22%), pyrexia (21%), and constipation (21%). The most common Grade 3–4 adverse reactions (≥ 2%) were urinary tract infection, anemia, fatigue, dehydration, intestinal obstruction, urinary obstruction, hematuria, dyspnea, acute kidney injury, abdominal pain, venous thromboembolism, sepsis, and pneumonia.Three patients (0.9%) who were treated with TECENTRIQ experienced either sepsis, pneumonitis, or intestinal obstruction which led to death. TECENTRIQ was discontinued for adverse reactions in 3.2% (10/310) of the 310 patients. Sepsis led to discontinuation in 0.6% (2/310) of patients. Adverse reactions leading to interruption of TECENTRIQ occurred in 27% of patients; the most common (> 1%) were liver enzyme increase, urinary tract infection, diarrhea, fatigue, confusional state, urinary obstruction, pyrexia, dyspnea, venous thromboembolism, and pneumonitis. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions (> 2%) were urinary tract infection, hematuria, acute kidney injury, intestinal obstruction, pyrexia, venous thromboembolism, urinary obstruction, pneumonia, dyspnea, abdominal pain, sepsis, and confusional state. Table 1 summarizes the adverse reactions that occurred in ≥ 10% of patients while Table 2 summarizes Grade 3–4 selected laboratory abnormalities that occurred in ≥ 1% of patients treated with TECENTRIQ in Cohort 2 of Study 1.

Table 1: All Grade Adverse Reactions in ≥ 10% of Patients with Urothelial Carcinoma in Study 1

TECENTRIQ N = 310

Adverse Reaction All Grades (%) Grades 3–4 (%)

All Adverse Reactions 96 50

Gastrointestinal Disorders

Nausea 25 2

Constipation 21 0.3

Diarrhea 18 1

Abdominal pain 17 4

Vomiting 17 1

S:7”

S:10”

T:7.75”

T:10.5”

82524ha_a.indd 2 10/22/16 4:49 PM

6 | Oncologistics Oncologistics | 7

Table of Contentswinter 2016-17

8 Plugging Profit Leaks

By Alana Vaughn

16 Reimbursement Watch

How the Repeal of Healthcare Reform Might Play

Out and How it Could Impact You

By Xcenda

24 Eye on ION

The Metamorphosis of a Community Oncology

Practice

As told by Dr. Tracey Weisberg

29 What’s News at ION

volume 15, issue 4 - winter 2016-17

Editorial & Design staff:

· Chris Vorce Senior Director, Marketing & Communications, ION Solutions

· Tricia Musslewhite Manager, Marketing & Communications, ION Solutions

· Sylvia Mugica Manager, Graphic Design, ION Solutions

oncologisticsION Solutions article and advertising submissions:

Article submissions and suggestions, as well as advertising inquiries, may be sent to:

Tricia MusslewhiteManaging Editor, Oncologisticsc/o ION Solutions3101 Gaylord ParkwayFrisco, TX 75034

Information presented in Oncologistics is not intended as a substitute for the personalized advice given by a healthcare provider. The opinions expressed on the pages of Oncologistics magazine are those of the authors and do not necessarily reflect the views of ION Solutions or AmerisourceBergen Specialty Group. Although Oncologistics strives to present only current and accurate information, readers should not consider it as professional advice or endorsement of any position. Although great care has been taken in compiling and checking the information given in this publication to ensure accuracy, the authors, ION Solutions, and its employees or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions, or inaccuracies in this magazine, whether arising from negligence or otherwise or for any consequence arising therefrom. The staff of Oncologistics provides columns and other editorial support. In no way are they responsible for the specific views presented in Oncologistics. Oncologistics magazine is published by ION Solutions, an AmerisourceBergen Specialty Group company.

All archived issues of Oncologistics are available online at www.iononline.com.

oneononewith Mark Santos

“We have a voice. As community oncologists, we need to use our voice to be present for both our patients and fellow physicians.” Dr. Tracey Weisberg, president and lead physician at New England Cancer Specialists, makes this statement in the story on page 24 about the transformation of her community oncology practice. In 2016, community oncologists, ION Solutions and many partners worked together and spoke up for the betterment of your patients and your practices.

In December 2016, CMS cancelled the proposed Medicare Part B Drug Payment Model. Shortly before that, CVS reversed its decision to block oncology clinics dispensing patients’ drugs. Community oncologists raised a number of concerns about these proposals, and the supporters decided not to move forward. With all of the pressures on oncology practices today, it is imperative that we continue to use our voices to maintain the viability of community oncology.

In 2017 physician practices will prepare for value-based reimbursement and continue to make their practices as efficient as possible. On page eight, Business Coach Alana Vaughn shares useful approaches to optimize an oncology practice’s operations and boost its bottom line.

Thank you for your continued partnership. We are committed to offering you creative GPO partnering and contracting, educational events, practice advocacy and practice management resources. We look forward to continuing to do so in 2017.

Mark SantosPresident, ION GPO

8 | Oncologistics Oncologistics | 9

Plugging Profit LeaksA former practice administrator’s take on maximizing oncology practice revenuesBy Alana Vaughn

Savvy oncology practices that leverage a range of tools

and information will benefit from more efficient decision

making and a healthier financial picture.

Like a slowly dripping faucet or an improperly insulated window, gaps and inefficiencies in a business allow profits to seep out over time. Even one leak—while seemingly small—can have damaging effects on a company’s financial health. Oncology practices are no different.

Drug inventory, billing and reimbursement methods, and operational efficiency are the areas of an oncology practice most likely to fall victim to these profit “leaks.” But with so many areas of the business vying for attention, sometimes it’s a simple question of where to start.

As practice administrator in Baton Rouge, La., for a decade and a half, I experienced firsthand the growing pains of a community oncology practice. During my tenure, I identified and implemented myriad incremental improvements and adjustments to help the oncologists keep their number one priority in sight: directing patients on the path to better health.

Now, as a business coach for Innovation Cancer, my role is all about helping practices realize opportunities for improved efficiencies and growth using our technology and resources and my experience managing a practice. I draw on my background to help practices across the nation uncover new ways to grow and expand while avoiding common profit leaks that financially strain the practice and its staff. Here are a few approaches I’ve picked up to plug profit leaks and optimize an oncology practice’s operations.

Overhaul drug inventory

The medications that comprise a practice’s inventory should be viewed as assets that will be converted into cash—and the sooner that happens, the better.

■ Understand inventory’s financial role in the business. Drug inventory is known as the oncology practice’s financial backbone. In fact, in 2007 nearly 80 percent of oncology practice revenue came from the buying and billing of drugs.1

■ Maintain a low inventory. Ordering drugs once a week may seem easier and less taxing on resources than ordering more frequently, but it’s akin to throwing money out an open window.

■ Order products on demand. With the right knowledge, a one-time adjustment could translate into a six-figure savings for a small oncology practice. The money saved by ordering drugs on demand can be redirected to pay bills, reinvest in the practice or negotiate better payment terms with the distributor by paying invoices earlier.

1Journal of Oncology Practice. The 2007 National Practice Benchmark. 2008. Accessed 2 August 2016. Available online at http://jop.ascopubs.org/content/4/4/178.full.

10 | Oncologistics Oncologistics | 11

Button up billing and collections

Improvements to revenue cycle management can substantially alter a practice’s financial picture, so long as the same level of scrutiny as managing drug inventory is applied.

■ Reviewing and reconciling bills requires rigor and discipline. Billing and collections procedures and documents must be routinely mined for costly mistakes, keeping in mind that mistakes can occur on both the payer and provider sides. At a minimum, metrics to monitor include number of open claims, patient volume, conversion factor and claims being reimbursed at 100 percent.

■ Use a fine-toothed comb on insurance claims. A practice might be able to implement changes that bring in more money by identifying common patterns in insurance denials.

■ Are your bills ending up in patients’ trash cans? Following up on patients’ financial responsibilities is another area that often does not see enough follow-through. Is the practice collecting all co-pays? What system is in place to collect the rest of a patient’s payment? Are payments being collected in a timely manner?

■ Adjust the AR timeline. Reducing outstanding accounts receivable days is vital to maintaining a healthy bottom line. It is important to submit charges 24-48 hours from the date of service, as delays in claim submission mean delays in receiving payment.

Trust technology as a valuable team member

Savvy oncology practices that leverage a range of tools and information will benefit from more efficient decision making and a healthier financial picture. Often, the biggest hurdle is trusting the technology to effectively do what was once a human task.

■ Upgrade and integrate technologies. Practice management software, inventory cabinets and electronic health record (EHR) solutions can assume some of the burden of the practice’s workflow tasks. A sophisticated practice management system paired with a specialty EHR can save practice staff time and improve output.

■ Instill better inventory management habits. Industry tools can help by reporting practice inventory levels, peer levels and revealing the potential savings incurred by remaining at that level or adopting best practices.

■ Identify lost opportunities. Business intelligence tools and inventory cabinets can keep a practice on track and save valuable time formerly spent on manual data entry. The practice can free up funds by knowing exactly how many drugs are stocked, saving precious funds often given to a third party to perform the same task.

■ Analyze and manipulate data. Utilizing financial analytics tools, a practice can pull data directly out of its practice management system to benchmark coding patterns and other areas for improvement.

■ Link the practice’s software. An automated inventory system can link up with practice management (PM) software to automatically bill for each drug ordered. In addition, it is important for practices to link their EMR and PM systems. Many practices bill out of the interface between their EMR and PM and then take a feed from the inventory system to compare billing.

■ Enlist tech that can mind the gaps. There are a number of other tools that can help practices find lost revenue without losing manpower. These include technology that calculates patient financial responsibility, identifies patient assistance funds or reviews treatment regimen profitability.

Maximize all opportunities

Once the inventory and billing and collections processes are up to snuff, practices might consider looking for other areas that leak profits. With a little creativity and ingenuity, practices can learn to pinpoint and streamline problem spots to increase efficiencies, optimize operations and maintain regulatory compliance.

■ Focus on inventory consolidation. To ensure savings for the practice and its patients, practice administrators can search for less expensive equivalents of drugs purchased on a regular basis.

■ Search for hidden goldmines. Dedicate one staff member’s oversight to staying up to date on rebates, coupons and other discounts.

With the right knowledge, a one-

time adjustment could translate

into six-figure savings for a small

oncology practice.

Alana Vaughn joined AmerisourceBergen in June 2015 as a business coach for Innovation Cancer. In this role, she works closely with oncology practices (practice administrators, nursing staff and business staff) and the Innovation Cancer team to ensure practices

are operating at maximum efficiency through the utilization of best-in-class technology solutions, data analysis and process reviews.

■ Follow the letter of the law. Being vigilant about the latest regulatory changes to reimbursement structures can ensure a practice remains compliant and maximizes the payments available.

■ Err on the safe side. Sometimes it’s not about plugging a leak but heading off a potentially costly mistake before it occurs. For example, when a practice obtains a drug from the manufacturer free of cost, it must catalogue that product as a free drug in the billing system.

Streamline internal processes

Reassessing a practice’s processes can free up valuable employee time that can be redirected to enhance patient care, thereby improving clinical operations and possibly even increasing revenue.

■ Paper is out. Maintaining manual and paper-based billing and inventory mechanisms is double the work and half as productive.

■ Exercise smart staffing. A comprehensive view of the practice’s staffing model may reveal roles that could be automated or consolidated, but cutting staff isn’t always the answer. Where it makes sense, staff members can be trained in new roles that improve both efficiencies and the patient experience. By strategizing its staffing plan, a practice can gain efficiencies and open the revenue floodgates. For example, some practices are expanding the patient assistance program role to generate revenue for the practice and improve the patient experience.

■ Involve everyone. Even physicians can get involved in improving efficiencies. Savvy practice administrators pull data from their inventory cabinets and practice management systems, and then pull their physicians in to review whole episodes of care. The practice staff can collaborate to segment patient data by diagnosis, demographic information and treatment to see where outcomes are continually improving.

Learning to diagnose and fix profit leaks doesn’t have to be an overwhelming endeavor. Start by identifying the largest profit leak in the practice and taking it one day, and one step, at a time. Through better use of technology, implementing improved processes or revamping its approach to drug inventory, a community oncology practice can successfully plug profit leaks and boost its bottom line. ◾

AmerisourceBergen has recently launched Innovation Cancer, a national community of independent oncologists that utilizes business intelligence tools and other resources to enable greater focus on quality care. Innovation Cancer offers business coaching by experienced industry professionals, analytic tools designed to improve practice efficiency and access to turnkey marketing resources built to drive an increase in patient engagement and referrals for member practices. To learn more about Innovation Cancer, please email us at info@innovationcancer.com.

Takeda Oncology and are registered trademarks of Takeda Pharmaceutical Company Limited. NINLARO is a registered trademark of Millennium Pharmaceuticals, Inc.

Copyright © 2016, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA 7/16 USO/IXA/16/0157

Now under contract with your GPOLearn more about NINLARO at NINLAROhcp.com.

TOURMALINE-MM1: a global, phase 3, randomized (1:1), double-blind, placebo-controlled study that evaluated the safety and e� cacy of NINLARO (an oral proteasome inhibitor) vs placebo, both in combination with lenalidomide and dexamethasone, until disease progression or unacceptable toxicity in 722 patients with relapsed and/or refractory multiple myeloma who received 1-3 prior therapies.

Depth of response in the NINLARO and placebo regimens• ORR*: 78% vs 72%; CR: 12% vs 7%; VGPR+CR: 48% vs 39%; and PR: 30% vs 33%, respectively

The NINLARO regimen demonstrated rapid responses

Median time to initial response (months)

1.9

1.1

Placebo+len+dex

NINLARO regimen

EXTEND EFFICACY. EXTEND THE POSSIBILITIES.The approval of the NINLARO® (ixazomib) regimen (NINLARO+lenalidomide+dexamethasone) was based on a statistically signifi cant ~6 month improvement in median progression-free survival vs the placebo regimen (placebo+lenalidomide+dexamethasone) (median: 20.6 vs 14.7 months [95% CI, 17.0-NE and 95% CI, 12.9-17.6, respectively]; HR=0.74 [95% CI, 0.587-0.939]; P=0.012).

*ORR=CR+PR, including VGPR.ARs=adverse reactions; CR=complete response; ORRs=overall response rates; PR=partial response; VGPR=very good partial response.

IMPORTANT SAFETY INFORMATION FOR NINLARO

• Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.

• Peripheral Edema was reported with NINLARO. Monitor for fl uid retention. Investigate for underlying causes when appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms.

WARNINGS AND PRECAUTIONS• Thrombocytopenia has been reported with NINLARO.

During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the fi rst three cycles. Manage thrombocytopenia with dose modifi cations and platelet transfusions as per standard medical guidelines. Adjust dosing as needed. Platelet nadirs occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle.

• Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for severe symptoms.

INDICATION: NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

WARNINGS AND PRECAUTIONS (continued)• Cutaneous Reactions: Rash, most commonly maculo-

papular and macular rash, was reported with NINLARO. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modifi cation.

• Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly during treatment and adjust dosing as needed.

• Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an additional 90 days after the fi nal dose of NINLARO.

ADVERSE REACTIONSThe most common adverse reactions (≥ 20%) in the NINLARO regimen and greater than the placebo regimen, respectively, were diarrhea (42%, 36%), constipation (34%, 25%), thrombocytopenia (78%, 54%; pooled from adverse events and laboratory data), peripheral neuropathy (28%, 21%), nausea (26%, 21%), peripheral edema (25%, 18%), vomiting (22%, 11%), and back pain (21%, 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%).

SPECIAL POPULATIONS• Hepatic Impairment: Reduce the NINLARO starting dose to

3 mg in patients with moderate or severe hepatic impairment.• Renal Impairment: Reduce the NINLARO starting dose to

3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable.

• Lactation: Advise women to discontinue nursing while on NINLARO.

DRUG INTERACTIONS: Avoid concomitant administration of NINLARO with strong CYP3A inducers.

Please see adjacent Brief Summary.

REFERENCE: 1. Data on File 117, Takeda Pharmaceuticals International Co.

The NINLARO regimen represented a sustainable treatment for patients

Discontinuation rates of the full regimen due to ARs1

13% 11%NINLARO regimen

(n=360)Placebo+len+dex

(n=360)

Discontinuation rates were low and comparable with the NINLARO

and placebo regimens.

80% of patients continued at the starting dose of NINLARO without dose reduction1

Pooled hematologic adverse events and laboratory data• Incidence of thrombocytopenia in patients in the

NINLARO and placebo regimens: all grades, 78% and 54%; grades 3-4, 26% vs 11%, respectively

• Incidence of neutropenia: all grades, 67% vs 66%; grades 3-4, 26% vs 30%, respectively

†Represents a pooling of preferred terms.

Nonhematologic ARs occurring in ≥5% of patients with a ≥5% di� erence between the NINLARO regimen (n=360) and the placebo regimen (n=360)• All grades, grade 3 (respectively): upper respiratory

(19%, <1% vs 14%, <1%), peripheral neuropathies† (28%, 2% vs 21%, 2%), diarrhea (42%, 6% vs 36%, 2%), constipation (34%, <1% vs 25%, <1%), nausea (26%, 2% vs 21%, 0%), vomiting (22%, 1% vs 11%, <1%), rash† (19%, 3% vs 11%, 1%), back pain (21%, <1% vs 16%, 3%), peripheral edema (25%, 2% vs 18%, 1%)

• Grade 4 ARs occurring in ≥5% of patients with a ≥5% di± erence between the 2 regimens were 0%

IXAZ16CDNY5936_ION_JA_Sept2016_r4.indd All Pages 8/1/16 2:10 PM

Takeda Oncology and are registered trademarks of Takeda Pharmaceutical Company Limited. NINLARO is a registered trademark of Millennium Pharmaceuticals, Inc.

Copyright © 2016, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA 7/16 USO/IXA/16/0157

Now under contract with your GPOLearn more about NINLARO at NINLAROhcp.com.

TOURMALINE-MM1: a global, phase 3, randomized (1:1), double-blind, placebo-controlled study that evaluated the safety and e� cacy of NINLARO (an oral proteasome inhibitor) vs placebo, both in combination with lenalidomide and dexamethasone, until disease progression or unacceptable toxicity in 722 patients with relapsed and/or refractory multiple myeloma who received 1-3 prior therapies.

Depth of response in the NINLARO and placebo regimens• ORR*: 78% vs 72%; CR: 12% vs 7%; VGPR+CR: 48% vs 39%; and PR: 30% vs 33%, respectively

The NINLARO regimen demonstrated rapid responses

Median time to initial response (months)

1.9

1.1

Placebo+len+dex

NINLARO regimen

EXTEND EFFICACY. EXTEND THE POSSIBILITIES.The approval of the NINLARO® (ixazomib) regimen (NINLARO+lenalidomide+dexamethasone) was based on a statistically signifi cant ~6 month improvement in median progression-free survival vs the placebo regimen (placebo+lenalidomide+dexamethasone) (median: 20.6 vs 14.7 months [95% CI, 17.0-NE and 95% CI, 12.9-17.6, respectively]; HR=0.74 [95% CI, 0.587-0.939]; P=0.012).

*ORR=CR+PR, including VGPR.ARs=adverse reactions; CR=complete response; ORRs=overall response rates; PR=partial response; VGPR=very good partial response.

IMPORTANT SAFETY INFORMATION FOR NINLARO

• Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.

• Peripheral Edema was reported with NINLARO. Monitor for fl uid retention. Investigate for underlying causes when appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms.

WARNINGS AND PRECAUTIONS• Thrombocytopenia has been reported with NINLARO.

During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the fi rst three cycles. Manage thrombocytopenia with dose modifi cations and platelet transfusions as per standard medical guidelines. Adjust dosing as needed. Platelet nadirs occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle.

• Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for severe symptoms.

INDICATION: NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

WARNINGS AND PRECAUTIONS (continued)• Cutaneous Reactions: Rash, most commonly maculo-

papular and macular rash, was reported with NINLARO. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modifi cation.

• Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly during treatment and adjust dosing as needed.

• Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an additional 90 days after the fi nal dose of NINLARO.

ADVERSE REACTIONSThe most common adverse reactions (≥ 20%) in the NINLARO regimen and greater than the placebo regimen, respectively, were diarrhea (42%, 36%), constipation (34%, 25%), thrombocytopenia (78%, 54%; pooled from adverse events and laboratory data), peripheral neuropathy (28%, 21%), nausea (26%, 21%), peripheral edema (25%, 18%), vomiting (22%, 11%), and back pain (21%, 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%).

SPECIAL POPULATIONS• Hepatic Impairment: Reduce the NINLARO starting dose to

3 mg in patients with moderate or severe hepatic impairment.• Renal Impairment: Reduce the NINLARO starting dose to

3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable.

• Lactation: Advise women to discontinue nursing while on NINLARO.

DRUG INTERACTIONS: Avoid concomitant administration of NINLARO with strong CYP3A inducers.

Please see adjacent Brief Summary.

REFERENCE: 1. Data on File 117, Takeda Pharmaceuticals International Co.

The NINLARO regimen represented a sustainable treatment for patients

Discontinuation rates of the full regimen due to ARs1

13% 11%NINLARO regimen

(n=360)Placebo+len+dex

(n=360)

Discontinuation rates were low and comparable with the NINLARO

and placebo regimens.

80% of patients continued at the starting dose of NINLARO without dose reduction1

Pooled hematologic adverse events and laboratory data• Incidence of thrombocytopenia in patients in the

NINLARO and placebo regimens: all grades, 78% and 54%; grades 3-4, 26% vs 11%, respectively

• Incidence of neutropenia: all grades, 67% vs 66%; grades 3-4, 26% vs 30%, respectively

†Represents a pooling of preferred terms.

Nonhematologic ARs occurring in ≥5% of patients with a ≥5% di� erence between the NINLARO regimen (n=360) and the placebo regimen (n=360)• All grades, grade 3 (respectively): upper respiratory

(19%, <1% vs 14%, <1%), peripheral neuropathies† (28%, 2% vs 21%, 2%), diarrhea (42%, 6% vs 36%, 2%), constipation (34%, <1% vs 25%, <1%), nausea (26%, 2% vs 21%, 0%), vomiting (22%, 1% vs 11%, <1%), rash† (19%, 3% vs 11%, 1%), back pain (21%, <1% vs 16%, 3%), peripheral edema (25%, 2% vs 18%, 1%)

• Grade 4 ARs occurring in ≥5% of patients with a ≥5% di± erence between the 2 regimens were 0%

IXAZ16CDNY5936_ION_JA_Sept2016_r4.indd All Pages 8/1/16 2:10 PM

Brief Summary (cont’d)

Table 5: Thrombocytopenia and Neutropenia (pooled adverse event and laboratory data)

NINLARO + Lenalidomide and Dexamethasone

N=360

Placebo + Lenalidomide and Dexamethasone

N=360

N (%) N (%)

Any Grade Grade 3-4 Any Grade Grade 3-4

Thrombocytopenia 281 (78) 93 (26) 196 (54) 39 (11)

Neutropenia 240 (67) 93 (26) 239 (66) 107 (30)

Eye DisordersEye disorders were reported with many different preferred terms but in aggregate, the frequency was 26% in patients in the NINLARO regimen and 16% of patients in the placebo regimen. The most common adverse reactions were blurred vision (6% in the NINLARO regimen and 3% in the placebo regimen), dry eye (5% in the NINLARO regimen and 1% in the placebo regimen), and conjunctivitis (6% in the NINLARO regimen and 1% in the placebo regimen). Grade 3 adverse reactions were reported in 2% of patients in the NINLARO regimen and 1% in the placebo regimen.The following serious adverse reactions have each been reported at a frequency of < 1%: acute febrile neutrophilic dermatosis (Sweet’s syndrome), Stevens-Johnson syndrome, transverse myelitis, posterior reversible encephalopathy syndrome, tumor lysis syndrome, and thrombotic thrombocytopenic purpura.7 DRUG INTERACTIONS7.1 Strong CYP3A Inducers: Avoid concomitant administration of NINLARO with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John’s Wort).8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy: Women should avoid becoming pregnant while being treated with NINLARO.Risk Summary: NINLARO can cause fetal harm when administered to a pregnant woman. There are no human data available regarding the potential effect of NINLARO on pregnancy or development of the embryo or fetus. Ixazomib caused embryo-fetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose. Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with NINLARO. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Animal Data: In an embryo-fetal development study in pregnant rabbits there were increases in fetal skeletal variations/abnormalities (caudal vertebrae, number of lumbar vertebrae, and full supernumerary ribs) at doses that were also maternally toxic (≥ 0.3 mg/kg). Exposures in the rabbit at 0.3 mg/kg were 1.9 times the clinical time averaged exposures at the recommended dose of 4 mg. In a rat dose range-finding embryo-fetal development study, at doses that were maternally toxic, there were decreases in fetal weights, a trend towards decreased fetal viability, and increased post-implantation losses at 0.6 mg/kg. Exposures in rats at the dose of 0.6 mg/kg was 2.5 times the clinical time averaged exposures at the recommended dose of 4 mg.8.2 Lactation: It is not known whether NINLARO or its metabolites are present in human milk. Many drugs are present in human milk and as a result, there could be a potential for adverse events in nursing infants. Advise women to discontinue nursing.8.3 Females and Males of Reproductive Potential: Contraception - Male and female patients of childbearing potential must use effective contraceptive measures during and for 90 days following treatment. Infertility - Fertility studies were not conducted with NINLARO; however there were no effects on reproductive organs in either males or females in nonclinical studies in rats and dogs.8.4 Pediatric Use: Safety and effectiveness have not been established in pediatric patients.8.5 Geriatric Use: Of the total number of subjects in clinical studies of NINLARO, 55% were 65 and over, while 17% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.8.6 Hepatic Impairment: In patients with moderate or severe hepatic impairment, the mean AUC increased by 20% when compared to patients with normal hepatic function. Reduce the starting dose of NINLARO in patients with moderate or severe hepatic impairment.

8.7 Renal Impairment: In patients with severe renal impairment or ESRD requiring dialysis, the mean AUC increased by 39% when compared to patients with normal renal function. Reduce the starting dose of NINLARO in patients with severe renal impairment or ESRD requiring dialysis. NINLARO is not dialyzable and therefore can be administered without regard to the timing of dialysis.10 OVERDOSAGE: There is no known specific antidote for NINLARO overdose. In the event of an overdose, monitor the patient for adverse reactions and provide appropriate supportive care.17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Patient Information).Dosing Instructions• Instruct patients to take NINLARO exactly as prescribed.• Advise patients to take NINLARO once a week on the same day and at

approximately the same time for the first three weeks of a four week cycle.• Advise patients to take NINLARO at least one hour before or at least two

hours after food.• Advise patients that NINLARO and dexamethasone should not be taken at the

same time, because dexamethasone should be taken with food and NINLARO should not be taken with food.

• Advise patients to swallow the capsule whole with water. The capsule should not be crushed, chewed or opened.

• Advise patients that direct contact with the capsule contents should be avoided. In case of capsule breakage, avoid direct contact of capsule contents with the skin or eyes. If contact occurs with the skin, wash thoroughly with soap and water. If contact occurs with the eyes, flush thoroughly with water.

• If a patient misses a dose, advise them to take the missed dose as long as the next scheduled dose is ≥ 72 hours away. Advise patients not to take a missed dose if it is within 72 hours of their next scheduled dose.

• If a patient vomits after taking a dose, advise them not to repeat the dose but resume dosing at the time of the next scheduled dose.

• Advise patients to store capsules in original packaging, and not to remove the capsule from the packaging until just prior to taking NINLARO.

Thrombocytopenia: Advise patients that they may experience low platelet counts (thrombocytopenia). Signs of thrombocytopenia may include bleeding and easy bruising.Gastrointestinal Toxicities: Advise patients they may experience diarrhea, constipation, nausea and vomiting and to contact their physician if these adverse reactions persist.Peripheral Neuropathy: Advise patients to contact their physicians if they experience new or worsening symptoms of peripheral neuropathy such as tingling, numbness, pain, a burning feeling in the feet or hands, or weakness in the arms or legs.Peripheral Edema: Advise patients to contact their physicians if they experience unusual swelling of their extremities or weight gain due to swelling.Cutaneous Reactions: Advise patients to contact their physicians if they experience new or worsening rash.Hepatotoxicity: Advise patients to contact their physicians if they experience jaundice or right upper quadrant abdominal pain.Pregnancy: Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with NINLARO and for 90 days following the final dose. Advise patients to contact their physicians immediately if they or their female partner become pregnant during treatment or within 90 days of the final dose.Concomitant Medications: Advise patients to speak with their physicians about any other medication they are currently taking and before starting any new medications.

Please see full Prescribing Information for NINLARO at NINLARO-hcp.com.

NINLARO is a registered trademark of Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

©2016 Millennium Pharmaceuticals, Inc.20160209 v2 USO/IXA/15/0123(2)

BRIEF SUMMARY OF PRESCRIBING INFORMATIONNINLARO (ixazomib) capsules, for oral use

1 INDICATIONNINLARO (ixazomib) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.5 WARNINGS AND PRECAUTIONS5.1 Thrombocytopenia: Thrombocytopenia has been reported with NINLARO with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. Three percent of patients in the NINLARO regimen and 1% of patients in the placebo regimen had a platelet count ≤ 10,000/mm3 during treatment. Less than 1% of patients in both regimens had a platelet count ≤ 5000/mm3 during treatment. Discontinuations due to thrombocytopenia were similar in both regimens (< 1% of patients in the NINLARO regimen and 2% of patients in the placebo regimen discontinued one or more of the three drugs). The rate of platelet transfusions was 6% in the NINLARO regimen and 5% in the placebo regimen. Monitor platelet counts at least monthly during treatment with NINLARO. Consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines.5.2 Gastrointestinal Toxicities: Diarrhea, constipation, nausea, and vomiting, have been reported with NINLARO, occasionally requiring use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea was reported in 42% of patients in the NINLARO regimen and 36% in the placebo regimen, constipation in 34% and 25%, respectively, nausea in 26% and 21%, respectively, and vomiting in 22% and 11%, respectively. Diarrhea resulted in discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for Grade 3 or 4 symptoms.5.3 Peripheral Neuropathy: The majority of peripheral neuropathy adverse reactions were Grade 1 (18% in the NINLARO regimen and 14% in the placebo regimen) and Grade 2 (8% in the NINLARO regimen and 5% in the placebo regimen). Grade 3 adverse reactions of peripheral neuropathy were reported at 2% in both regimens; there were no Grade 4 or serious adverse reactions.The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimen, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Patients should be monitored for symptoms of neuropathy. Patients experiencing new or worsening peripheral neuropathy may require dose modification.5.4 Peripheral Edema: Peripheral edema was reported in 25% and 18% of patients in the NINLARO and placebo regimens, respectively. The majority of peripheral edema adverse reactions were Grade 1 (16% in the NINLARO regimen and 13% in the placebo regimen) and Grade 2 (7% in the NINLARO regimen and 4% in the placebo regimen).Grade 3 peripheral edema was reported in 2% and 1% of patients in the NINLARO and placebo regimens, respectively. There was no Grade 4 peripheral edema reported. There were no discontinuations reported due to peripheral edema. Evaluate for underlying causes and provide supportive care, as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms.5.5 Cutaneous Reactions: Rash was reported in 19% of patients in the NINLARO regimen and 11% of patients in the placebo regimen. The majority of the rash adverse reactions were Grade 1 (10% in the NINLARO regimen and 7% in the placebo regimen) or Grade 2 (6% in the NINLARO regimen and 3% in the placebo regimen). Grade 3 rash was reported in 3% of patients in the NINLARO regimen and 1% of patients in the placebo regimen. There were no Grade 4 or serious adverse reactions of rash reported. The most common type of rash reported in both regimens included maculo-papular and macular rash. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification if Grade 2 or higher.5.6 Hepatotoxicity: Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms.5.7 Embryo-Fetal Toxicity: NINLARO can cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings in animals. There are no adequate and well-controlled studies in pregnant women using NINLARO. Ixazomib caused embryo-fetal toxicity in pregnant rats and

rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose.Females of reproductive potential should be advised to avoid becoming pregnant while being treated with NINLARO. If NINLARO is used during pregnancy or if the patient becomes pregnant while taking NINLARO, the patient should be apprised of the potential hazard to the fetus. Advise females of reproductive potential that they must use effective contraception during treatment with NINLARO and for 90 days following the final dose.6 ADVERSE REACTIONSThe following adverse reactions are described in detail in other sections of the prescribing information:• Thrombocytopenia [see Warnings and Precautions (5.1)]• Gastrointestinal Toxicities [see Warnings and Precautions (5.2)]• Peripheral Neuropathy [see Warnings and Precautions (5.3)]• Peripheral Edema [see Warnings and Precautions (5.4)]• Cutaneous Reactions [see Warnings and Precautions (5.5)]• Hepatotoxicity [see Warnings and Precautions (5.6)]6.1 CLINICAL TRIALS EXPERIENCEBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The safety population from the randomized, double-blind, placebo-controlled clinical study included 720 patients with relapsed and/or refractory multiple myeloma, who received NINLARO in combination with lenalidomide and dexamethasone (NINLARO regimen; N=360) or placebo in combination with lenalidomide and dexamethasone (placebo regimen; N=360).The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen and greater than the placebo regimen were diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, and back pain. Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.Table 4: Non-Hematologic Adverse Reactions Occurring in ≥ 5% of Patients with a ≥ 5% Difference Between the NINLARO Regimen and the Placebo Regimen (All Grades, Grade 3 and Grade 4)

NINLARO + Lenalidomide and Dexamethasone

N=360

Placebo + Lenalidomide and Dexamethasone

N=360

System Organ Class / Preferred Term N (%) N (%)

All Grade 3

Grade 4 All Grade

3Grade

4

Infections and infestationsUpper respiratory tract infection

69 (19) 1 (< 1) 0 52 (14) 2 (< 1) 0

Nervous system disordersPeripheral neuropathies* 100 (28) 7 (2) 0 77 (21) 7 (2) 0

Gastrointestinal disordersDiarrheaConstipationNauseaVomiting

151 (42)122 (34)92 (26)79 (22)

22 (6)1 (< 1)6 (2)4 (1)

0000

130 (36)90 (25)74 (21)38 (11)

8 (2)1 (< 1)

02 (< 1)

0000

Skin and subcutaneous tissue disorders

Rash* 68 (19) 9 (3) 0 38 (11) 5 (1) 0

Musculoskeletal and connective tissue disorders

Back pain 74 (21) 2 (< 1) 0 57 (16) 9 (3) 0

General disorders and administration site conditions

Edema peripheral 91 (25) 8 (2) 0 66 (18) 4 (1) 0

Note: Adverse reactions included as preferred terms are based on MedDRA version 16.0. *Represents a pooling of preferred terms

(Continued on next page)

16 | Oncologistics Oncologistics | 17

How the Repeal of Healthcare Reform Might Play Out And How it Could Impact YouBy Xcenda

The new Republican presidential administration and Republican majority in Congress are expected to bring major changes to healthcare in 2017, as candidates who campaigned on the promise of dismantling the Affordable Care Act (ACA) take office.

But big questions remain: What, if anything, will replace Obamacare? And how will it impact oncology and hematology practices and their patients and the healthcare industry as a whole?

In this issue, Reimbursement Watch takes a look at some of the possibilities and what is at stake.

Repealing Obamacare

In a largely symbolic exercise, Republicans in Congress already have voted to repeal the ACA more than 60 times. Each vote came with the knowledge that President Barack Obama would veto any repeal. In 2017, Republicans are likely to try to keep some aspects of the ACA that are extremely popular, such as:

■ Coverage for dependents until age 26

■ Ban on insurers excluding enrollees for pre-existing conditions

■ Increased incentives for health savings accounts

■ Efforts under Medicare to transition from fee-for-service to quality-driven payment systems

They also will most surely work to dismantle provisions that have been less popular with some conservatives, including:

■ Essential Health Benefits (EHB)

■ Individual and employer mandates

■ Medicaid expansion

■ Taxing the most-generous employer health benefit packages

■ Reductions on patient cost sharing

Left in the balance are millions of Americans who obtained coverage through Medicaid expansion and the exchanges. Just as critical to those patients receiving life-saving medical treatments are the doctors and healthcare institutions charged with providing their healthcare and whose viability relies on a sustainable business model.

What Happens Now?

Below are several key possible scenarios for repeal:

■ Lawmakers could delay any ACA repeal until after the 2018 mid-term elections in order to buy time to develop a replacement option. The downside is that this could create an unstable market for insurers, who would not be able to plan adequately or set premiums accordingly. Such a delay also could have a chilling effect on Americans enrolling in the exchange market, because they would not be sure their coverage would remain intact.

■ Any replacement for the ACA will take time to implement. Note that the exchanges did not take effect until four years after the ACA’s enactment. Republicans are being pressed into following a more-aggressive timeline than they would like. There is no clear replacement option that Republicans have agreed on. While still the President-

Reimbursement Watch elect, Donald Trump indicated that Rep. Tom Price would introduce a replacement plan as soon as he was confirmed as head of the Department of Health and Human Services. In the absence of broad consensus among the GOP, the ranks are showing divisions over how to handle the replacement. Some Republicans say they want a simultaneous repeal and replace effort with a two-year phase out and others are pushing for a longer phase out of three or four years. House Speaker Paul Ryan has said he plans to launch a concurrent repeal and replace “rescue mission for Americans from Obamacare.”

■ Because of the limitations around what can be accomplished through legislative reconciliation, Trump may use Executive Action to implement some changes. That adds another layer of uncertainty to the various repeal and replace scenarios.

What Else Does This Mean?

■ Republicans are likely to favor a private sector solution to replacing the ACA, such as offering federal dollars to drive enrollment in private commercial health plans.

■ With repeal, insurers would likely be able to pare down EHBs. Without basic coverage mandates, payers would likely design packages that offer minimal benefits and leave patients exposed to holes in coverage. This, paired with the prospect of states rolling back Medicaid expansion, would leave patients and providers vulnerable for more uncompensated care. However, dismantling the uniform requirements mandated by Essential Health Benefits could allow insurers to customize benefit packages that could better fit individual patient needs. That could potentially allow payers to offer sufficient coverage to customers at reduced costs. At the same time, beneficiaries will face a new reality where not everything they want in health insurance will be covered.

■ Pharmaceutical manufacturers will continue to be vilified over drug pricing. They also will be increasingly asked by patients, providers and payers to demonstrate that their products offer clinical advantages or cost differentiation. Manufacturers will have to balance these demands with

Left in the balance are millions

of Americans who obtained

coverage through Medicaid

expansion and the exchanges.

18 | Oncologistics Oncologistics | 19

the need for ongoing innovation in the development of new and improved therapies. The patient assistance and copay assistance programs offered by many manufacturers could become even more important to facilitating patient access to care if more Americans lose their health insurance coverage.

■ Medical providers can be expected to see more uninsured and underinsured patients in their practices as well as to field more patient questions about coverage. This will place an additional administrative burden on practice staff.

■ Conventional wisdom suggests that policy mechanisms such as the now-canceled Medicare Part B payment model and government price negotiation in Medicare are unlikely to be viable in a Republican-led Executive and Legislative branch. These and other price control measures could reemerge, but, for now anyway, that seems unlikely.

Final Thoughts

For 2017, Americans are still faced with high healthcare spending that is ratcheting up year over year – faster than the gross domestic product. The increase in spending is

pressuring state governments that must decide how to spend limited funds across healthcare, infrastructure and education. Employers are deciding between wage increases and premium subsidies. Practices have the difficult choice of treating uninsured and underinsured patients or referring them to safety net healthcare providers. Lastly, consumers continue to pay more in premiums and in out-of-pocket costs for their covered therapies as they are tasked with navigating a shifting coverage landscape.

As our experience with the ACA has shown, there is no single perfect solution to these challenges. America’s complex healthcare story will continue to unfold and each possible narrative bears close watching.

Medical providers can be expected to see more uninsured and underinsured patients in their practices as well as to field more patient questions about coverage.

NSCLC=non-small cell lung cancer.

PATIENTS WITH METASTATIC NSCLC NEED MORE POST- PLATINUM OPTIONS THAT CAN HELP TAKE CONTROL OF THEIR DISEASE THROUGH A SIGNIFICANT DELAY IN TUMOR GROWTH AND IMPROVED SURVIVAL.

WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, AND IMPAIRED WOUND HEALINGHemorrhage: CYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding.Gastrointestinal Perforation: CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.Impaired Wound Healing: Impaired wound healing can occur with antibodies inhibiting the VEGF pathway. Discontinue CYRAMZA therapy in patients with impaired wound healing. Withhold CYRAMZA prior to surgery and discontinue CYRAMZA if a patient develops wound healing complications.

Warnings and PrecautionsHemorrhage • CYRAMZA increased the risk of hemorrhage and gastrointestinal

hemorrhage, including severe and sometimes fatal hemorrhagic events. In study 3, which evaluated CYRAMZA plus docetaxel in metastatic non-small cell lung cancer (NSCLC), the incidence of severe bleeding was 2.4% for CYRAMZA plus docetaxel and 2.3% for placebo plus docetaxel. Patients with NSCLC receiving therapeutic anticoagulation or chronic therapy with NSAIDs or other antiplatelet therapy other than once-daily aspirin or with radiographic evidence of major airway or blood vessel invasion or intratumor cavitation were excluded from study 3; therefore, the risk of pulmonary hemorrhage in these groups of patients is unknown. Permanently discontinue CYRAMZA in patients who experience severe bleeding.

Arterial Thromboembolic Events (ATEs)• Serious, sometimes fatal, ATEs including myocardial infarction,

cardiac arrest, cerebrovascular accident, and cerebral ischemia occurred in clinical trials. Permanently discontinue CYRAMZA in patients who experience a severe ATE.

Hypertension• An increased incidence of severe hypertension occurred in patients

receiving CYRAMZA plus docetaxel (6%) as compared to placebo plus docetaxel (2%). Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every 2 weeks or more frequently as indicated during treatment. Temporarily suspend CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA if medically significant hypertension cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.

Infusion-Related Reactions (IRRs)• Prior to the institution of premedication recommendations across

clinical trials of CYRAMZA, IRRs occurred in 6 out of 37 patients (16%), including 2 severe events. The majority of IRRs across trials occurred during or following a first or second CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. Monitor patients during the infusion for signs and symptoms of IRRs in a setting with available resuscitation equipment. Immediately and permanently discontinue CYRAMZA for grade 3 or 4 IRRs.

Gastrointestinal Perforations• CYRAMZA is an antiangiogenic therapy that can increase the risk

of gastrointestinal perforation, a potentially fatal event. In study 3, the incidence of gastrointestinal perforation was 1% for CYRAMZA plus docetaxel versus 0.3% for placebo plus docetaxel. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.

Impaired Wound Healing• Impaired wound healing can occur with antibodies inhibiting the

VEGF pathway. CYRAMZA has not been studied in patients with serious or nonhealing wounds. CYRAMZA, as an antiangiogenic therapy, has the potential to adversely affect wound healing. Discontinue CYRAMZA therapy in patients with impaired wound healing. Withhold CYRAMZA prior to surgery. Resume CYRAMZA following the surgical intervention based on clinical judgment of adequate wound healing. If a patient develops wound healing complications during therapy, discontinue CYRAMZA until the wound is fully healed.

Clinical Deterioration in Child-Pugh B or C Cirrhosis• Clinical deterioration, manifested by new onset or worsening

encephalopathy, ascites, or hepatorenal syndrome, was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis only if the potential benefits of treatment are judged to outweigh the risks of clinical deterioration.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)• RPLS has been reported at a rate of <0.1% in clinical studies with

CYRAMZA. Confirm the diagnosis of RPLS with MRI and discontinue CYRAMZA in patients who develop RPLS. Symptoms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death.

Proteinuria Including Nephrotic Syndrome• Monitor proteinuria by urine dipstick and/or urinary protein

creatinine ratio for the development of worsening of proteinuria during CYRAMZA therapy. Withhold CYRAMZA for urine protein

levels that are ≥2 g over 24 hours. Reinitiate CYRAMZA at a reduced dose once the urine protein level returns to <2 g over 24 hours. Permanently discontinue CYRAMZA for urine protein levels >3 g over 24 hours or in the setting of nephrotic syndrome.

Thyroid Dysfunction• Monitor thyroid function during treatment with CYRAMZA. Embryofetal Toxicity• Based on its mechanism of action, CYRAMZA can cause fetal

harm when administered to pregnant women. Animal models link angiogenesis, VEGF, and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CYRAMZA and for at least 3 months after the last dose of CYRAMZA.

Most Common Adverse Reactions• The most commonly reported adverse reactions (all grades; grade

3/4) occurring in ≥5% of patients receiving CYRAMZA plus docetaxel and ≥2% higher than placebo plus docetaxel in study 3 were neutropenia (55% vs 46%; 49% vs 40%), fatigue/asthenia (55% vs 50%; 14% vs 11%), stomatitis/mucosal inflammation (37% vs 19%; 7% vs 2%), epistaxis (19% vs 7%; <1% vs <1%), febrile neutropenia (16% vs 10%; 16% vs 10%), peripheral edema (16% vs 9%; 0% vs <1%), thrombocytopenia (13% vs 5%; 3% vs <1%), lacrimation increased (13% vs 5%; <1% vs 0%), and hypertension (11% vs 5%; 6% vs 2%).

• The most common serious adverse events with CYRAMZA plus docetaxel in study 3 were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%). The use of granulocyte colony-stimulating factors was 42% in CYRAMZA plus docetaxel-treated patients versus 37% in patients who received placebo plus docetaxel.

• In patients ≥65 years of age, there were 18 (8%) deaths on treatment or within 30 days of discontinuation for CYRAMZA plus docetaxel and 9 (4%) deaths for placebo plus docetaxel. In patients <65 years of age, there were 13 (3%) deaths on treatment or within 30 days of discontinuation for CYRAMZA plus docetaxel and 26 (6%) deaths for placebo plus docetaxel.

• Treatment discontinuation due to adverse reactions occurred more frequently in CYRAMZA plus docetaxel-treated patients (9%) than in placebo plus docetaxel-treated patients (5%). The most common adverse events leading to treatment discontinuation of CYRAMZA were infusion-related reaction (0.5%) and epistaxis (0.3%).

• For patients with nonsquamous histology, the overall incidence of pulmonary hemorrhage was 7% and the incidence of grade ≥3 pulmonary hemorrhage was 1% for CYRAMZA plus docetaxel compared to 6% overall incidence and 1% for grade ≥3 pulmonary

hemorrhage for placebo plus docetaxel. For patients with squamous histology, the overall incidence of pulmonary hemorrhage was 10% and the incidence of grade ≥3 pulmonary hemorrhage was 2% for CYRAMZA plus docetaxel compared to 12% overall incidence and 2% for grade ≥3 pulmonary hemorrhage for placebo plus docetaxel.

• Clinically relevant adverse reactions reported in ≥1% and <5% of CYRAMZA plus docetaxel-treated patients in study 3 were hyponatremia (4.8% CYRAMZA plus docetaxel versus 2.4% for placebo plus docetaxel) and proteinuria (3.3% CYRAMZA plus docetaxel versus 0.8% placebo plus docetaxel).

Drug Interactions• No pharmacokinetic interactions were observed between

ramucirumab and docetaxel.

Use in Specific Populations• Pregnancy: Based on its mechanism of action, CYRAMZA can

cause fetal harm. Animal models link angiogenesis, VEGF, and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. There are no available data on CYRAMZA use in pregnant women to inform any drug-associated risks. No animal studies have been conducted to evaluate the effect of ramucirumab on reproduction and fetal development. Advise females of reproductive potential of the potential risk for maintaining pregnancy, risk to the fetus, and risk to newborn and infant development, and to use effective contraception during CYRAMZA therapy and for at least 3 months following the last dose of CYRAMZA.

• Lactation: Because of the potential risk for serious adverse reactions in nursing infants from ramucirumab, advise women that breastfeeding is not recommended during treatment with CYRAMZA.

• Females of Reproductive Potential: Advise females of reproductive potential that based on animal data CYRAMZA may impair fertility.

Please see Brief Summary of Prescribing Information for CYRAMZA, including Boxed Warnings for hemorrhage, gastrointestinal perforation, and impaired wound healing, on next page.RB-L HCP ISI 17SEP2015 References: 1. CYRAMZA (ramucirumab) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015. 2. Garon EB, Ciuleanu T-E, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673.PP-RB-US-0717 10/2016 PRINTED IN USA © Lilly USA, LLC 2016. All rights reserved.

CYRAMZA® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates.

IMPORTANT SAFETY INFORMATION FOR CYRAMZA

REVEL TRIAL DESIGN (N=1253)1

The phase III REVEL trial evaluated the efficacy and safety of CYRAMZA plus docetaxel vs placebo plus docetaxel in patients with metastatic NSCLC with disease progression on or after platinum-based chemotherapy. Major efficacy outcome measure was OS. Supportive efficacy outcome measures were PFS and ORR. All patients were required to have Eastern Cooperative Oncology Group performance status 0 or 1. Patients were randomized 1:1 (N=1253) to receive either CYRAMZA 10 mg/kg or placebo, in combination with docetaxel at 75 mg/m2 every 21 days.

HELP CONTROL THE DISEASE BY DELAYING TUMOR GROWTH, AS DEMONSTRATED BY A SIGNIFICANT IMPROVEMENT IN PFS AND ORR— BACKED BY IMPROVED OS1

OSMajor Outcome Measure (95% CI)§1

PFS=progression-free survival; ORR=objective response rate; OS=overall survival; CI=confidence interval.* The percentage of events at the time of analysis was 89% (558 patients) and 93% (583 patients) in the CYRAMZA and placebo arms, respectively.† Median.‡ Intent-to-treat (ITT) population. Disease progression and tumor response were assessed by investigators in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.2

ORR=complete + partial response; does not include stable disease.§ The percentage of deaths at the time of analysis was 68% (428 patients) and 73% (456 patients) in the CYRAMZA plus docetaxel and placebo plus docetaxel arms, respectively.

4.5 MONTHS†

3.0 MONTHS†

(4.2, 5.4) (2.8, 3.9)

VS

CYRAMZA + docetaxel

Placebo + docetaxel

10.5 MONTHS†

9.1 MONTHS†

(9.5, 11.2) (8.4, 10.0)

VS

CYRAMZA + docetaxel

Placebo + docetaxel

14%(11, 17)

VS23%(20, 26)

CYRAMZA + docetaxel

Placebo + docetaxel

Hazard ratio 0.76 (95% CI: 0.68, 0.86); P<0.001

Hazard ratio 0.86 (95% CI: 0.75, 0.98); P=0.024P<0.001

PFSSupportive Outcome Measure (95% CI)*1

ORRSupportive Outcome Measure (95% CI)‡1

CYRAMZA® (ramucirumab), in combination with docetaxel, is indicated for the treatment of patients with metastatic NSCLC with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.

IN METASTATIC NSCLCDELAY PROGRESSION, ADD TIME: MAKE AN IMPACT WITH CYRAMZA IN COMBINATION WITH DOCETAXEL

CYRAMZA CONTRACT EFFECTIVE APRIL 1, 2016

FIND OUT MORE

REVEL Trial Results

PATIENTONE Financial Assistance

RESOURCESfor Your Practice

Visit www.CYRAMZAHCP.com/Journal

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Adverse Reactions (MedDRA)System Organ Class

CYRAMZA plus docetaxel(N=627)

Placebo plus docetaxel(N=618)

All Grades(Frequency %)

Grade 3-4(Frequency %)

All Grades(Frequency %)

Grade 3-4(Frequency %)

Eye Disorders

Lacrimation increased 13 <1 5 0

General Disorders and Administration Site Disorders

Fatigue/Asthenia 55 14 50 11

Peripheral edema 16 0 9 <1

Respiratory, Thoracic, and Mediastinal Disorders

Epistaxis 19 <1 7 <1

Vascular Disorders

Hypertension 11 6 5 2

Clinically relevant adverse drug reactions reported in ≥1% and <5% of the CYRAMZA plus docetaxel-treated patients in Study 3 were hyponatremia (4.8% CYRAMZA plus docetaxel versus 2.4% for placebo plus docetaxel) and proteinuria (3.3% CYRAMZA plus docetaxel versus 0.8% placebo plus docetaxel).ImmunogenicityAs with all therapeutic proteins, there is the potential for immunogenicity. In 23 clinical trials, 86/2890 (3.0%) of CYRAMZA-treated patients tested positive for treatment-emergent anti-ramucirumab antibodies by an enzyme-linked immunosorbent assay (ELISA). Neutralizing antibodies were detected in 14 of the 86 patients who tested positive for treatment-emergent anti-ramucirumab antibodies.The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to CYRAMZA with the incidences of antibodies to other products may be misleading.

DRUG INTERACTIONSNo pharmacokinetic (PK) interactions were observed between ramucirumab and docetaxel.

USE IN SPECIFIC POPULATIONSPregnancyRisk SummaryBased on its mechanism of action, CYRAMZA can cause fetal harm. Animal models link angiogenesis, VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. There are no available data on CYRAMZA in pregnant women to inform any drug-associated risks. No animal studies have been conducted to evaluate the effect of ramucirumab on reproduction and fetal development. The background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Advise pregnant women of the potential risk to a fetus.Animal DataNo animal studies have been specifically conducted to evaluate the effect of ramucirumab on reproduction and fetal development. In mice, loss of the VEGFR2 gene resulted in embryofetal death and these fetuses lacked organized blood vessels and blood islands in the yolk sac. In other models, VEGFR2 signaling was associated with development and maintenance of endometrial and placental vascular function, successful blastocyst implantation, maternal and feto-placental vascular differentiation, and development during early pregnancy in rodents and non-human primates. Disruption of VEGF signaling has also been associated with developmental anomalies including poor development of the cranial region, forelimbs, forebrain, heart, and blood vessels.LactationRisk SummaryThere is no information on the presence of ramucirumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential risk for serious adverse reactions in nursing infants from ramucirumab, advise women that breastfeeding is not recommended during treatment with CYRAMZA.Females and Males of Reproductive PotentialContraceptionFemalesBased on its mechanism of action, CYRAMZA can cause fetal harm. Advise females of reproductive potential to use effective contraception while receiving CYRAMZA and for at least 3 months after the last dose of CYRAMZA.InfertilityFemalesAdvise females of reproductive potential that based on animal data CYRAMZA may impair fertility.Pediatric UseThe safety and effectiveness of CYRAMZA in pediatric patients have not been established. In animal studies, effects on epiphyseal growth plates were identified. In cynomolgus monkeys, anatomical pathology revealed adverse effects on the epiphyseal growth plate (thickening and osteochondropathy) at all doses tested (5-50 mg/kg). Ramucirumab exposure at the lowest weekly dose tested in the cynomolgus monkey was 0.2 times the exposure in humans at the recommended dose of ramucirumab as a single agent.Geriatric UseOf the 563 CYRAMZA-treated patients in two randomized gastric cancer clinical studies, 36% were 65 and over, while 7% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Of the 1253 patients in Study 3, 455 (36%) were 65 and over and 84 (7%) were 75 and over. Of the 627 patients who received CYRAMZA plus docetaxel in Study 3, 237 (38%) were 65 and over, while 45 (7%) were 75 and over. In an exploratory subgroup analysis of Study 3, the hazard ratio for overall survival in patients less than 65 years old was 0.74 (95% CI: 0.62, 0.87) and in patients 65 years or older was 1.10 (95% CI: 0.89, 1.36). Renal ImpairmentNo dose adjustment is recommended for patients with renal impairment based on population pharmacokinetic analysis.Hepatic ImpairmentNo dose adjustment is recommended for patients with mild (total bilirubin within upper limit of normal [ULN] and aspartate aminotransferase [AST] >ULN, or total bilirubin >1.0-1.5 times ULN and any AST)

or moderate (total bilirubin >1.5-3.0 times ULN and any AST) hepatic impairment based on population pharmacokinetic analysis. Clinical deterioration was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA.

DOSAGE AND ADMINISTRATION

Do not administer CYRAMZA as an intravenous push or bolus.

Recommended Dose and ScheduleThe recommended dose of CYRAMZA is 10 mg/kg administered by intravenous infusion over 60 minutes on day 1 of a 21-day cycle prior to docetaxel infusion. Continue CYRAMZA until disease progression or unacceptable toxicity.PremedicationPrior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine H1 antagonist (e.g., diphenhydramine hydrochloride). For patients who have experienced a Grade 1 or 2 infusion reaction, also premedicate with dexamethasone (or equivalent) and acetaminophen prior to each CYRAMZA infusion.Dose ModificationsInfusion-Related Reactions (IRR)• Reduce the infusion rate of CYRAMZA by 50% for Grade 1 or 2 IRRs.• Permanently discontinue CYRAMZA for Grade 3 or 4 IRRs.Hypertension• Interrupt CYRAMZA for severe hypertension until controlled with medical management.• Permanently discontinue CYRAMZA for severe hypertension that cannot be controlled with

antihypertensive therapy.Proteinuria• Interrupt CYRAMZA for urine protein levels ≥2 g/24 hours. Reinitiate treatment at a reduced dose

of 8 mg/kg every 3 weeks once the urine protein level returns to <2 g/24 hours. If the protein level ≥2 g/24 hours reoccurs, interrupt CYRAMZA and reduce the dose to 6 mg/kg every 3 weeks once the urine protein level returns to <2 g/24 hours.

• Permanently discontinue CYRAMZA for urine protein level >3 g/24 hours or in the setting of nephrotic syndrome.

Wound Healing Complications• Interrupt CYRAMZA prior to scheduled surgery until the wound is fully healed.Arterial Thromboembolic Events, Gastrointestinal Perforation, or Grade 3 or 4 Bleeding• Permanently discontinue CYRAMZA.

For toxicities related to docetaxel, refer to the current respective prescribing information.

PATIENT COUNSELING INFORMATION• Hemorrhage: Advise patients that CYRAMZA can cause severe bleeding. Advise patients to contact their health care provider for bleeding or symptoms of bleeding including lightheadedness. • Arterial thromboembolic events: Advise patients of an increased risk of an arterial thromboembolic event. • Hypertension: Advise patients to undergo routine blood pressure monitoring and to contact their health care provider if blood pressure is elevated or if symptoms from hypertension occur including severe headache, lightheadedness, or neurologic symptoms. • Gastrointestinal perforations: Advise patients to notify their health care provider for severe diarrhea, vomiting, or severe abdominal pain. • Impaired wound healing: Advise patients that CYRAMZA has the potential to impair wound healing. Instruct patients not to undergo surgery without first discussing this potential risk with their health care provider. • Pregnancy and fetal harm: Advise females of reproductive potential of the potential risk for maintaining pregnancy, risk to the fetus, and risk to postnatal newborn and infant development and to use effective contraception during CYRAMZA therapy and for at least 3 months following the last dose of CYRAMZA. • Lactation: Advise patients not to breastfeed during CYRAMZA treatment. • Infertility: Advise females of reproductive potential regarding potential infertility effects of CYRAMZA.

Additional information can be found at www.CYRAMZAhcp.com.

Eli Lilly and Company, Indianapolis, IN 46285, USACopyright © 2015, Eli Lilly and Company. All rights reserved.

RB-L HCP BS 04MAY2015

Table 4: Adverse Reactions Occurring at Incidence Rate ≥5% and a ≥2% Difference Between Arms in Patients Receiving CYRAMZA in Study 3 (Cont.)

CYRAMZA® (ramucirumab) injection RB-L HCP BS 04MAY2015 CYRAMZA® (ramucirumab) injection RB-L HCP BS 04MAY2015

CYRAMZA RB-L HCP BS 04MAY2015 - 7 x 10, 2 pages PRINTER VERSION 1 OF 2

CYRAMZA® (ramucirumab) injectionBRIEF SUMMARY: For complete safety, please consult the full Prescribing Information.

WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, AND IMPAIRED WOUND HEALINGHemorrhage: CYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding.

Gastrointestinal Perforation: CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.

Impaired Wound Healing: Impaired wound healing can occur with antibodies inhibiting the VEGF pathway. Discontinue CYRAMZA therapy in patients with impaired wound healing. Withold CYRAMZA prior to surgery and discontinue CYRAMZA if a patient develops wound healing complications.

INDICATIONS AND USAGENon-Small Cell Lung Cancer:CYRAMZA, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.

CONTRAINDICATIONSNone.

WARNINGS AND PRECAUTIONSHemorrhageCYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal hemorrhagic events. In Study 1, the incidence of severe bleeding was 3.4% for CYRAMZA and 2.6% for placebo. In Study 2, the incidence of severe bleeding was 4.3% for CYRAMZA plus paclitaxel and 2.4% for placebo plus paclitaxel. Patients with gastric cancer receiving nonsteroid anti-inflammatory drugs (NSAIDs) were excluded from enrollment in Studies 1 and 2; therefore, the risk of gastric hemorrhage in CYRAMZA-treated patients with gastric tumors receiving NSAIDs is unknown. In Study 3, the incidence of severe bleeding was 2.4% for CYRAMZA plus docetaxel and 2.3% for placebo plus docetaxel. Patients with NSCLC receiving therapeutic anticoagulation or chronic therapy with NSAIDS or other antiplatelet therapy other than once daily aspirin or with radiographic evidence of major airway or blood vessel invasion or intratumor cavitation were excluded from Study 3; therefore the risk of pulmonary hemorrhage in these groups of patients is unknown. In Study 4, the incidence of severe bleeding was 2.5% for CYRAMZA plus FOLFIRI and 1.7% for placebo plus FOLFIRI. Permanently discontinue CYRAMZA in patients who experience severe bleeding.Arterial Thromboembolic EventsSerious, sometimes fatal, arterial thromboembolic events (ATEs) including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia occurred in clinical trials including 1.7% of 236 patients who received CYRAMZA as a single agent for gastric cancer in Study 1. Permanently discontinue CYRAMZA in patients who experience a severe ATE.HypertensionAn increased incidence of severe hypertension occurred in patients receiving CYRAMZA as a single agent (8%) as compared to placebo (3%) and in patients receiving CYRAMZA plus paclitaxel (15%) as compared to placebo plus paclitaxel (3%), in patients receiving CYRAMZA plus docetaxel (6%) as compared to placebo plus docetaxel (2%), and in patients receiving CYRAMZA plus FOLFIRI (11%) as compared to placebo plus FOLFIRI (3%). Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every two weeks or more frequently as indicated during treatment. Temporarily suspend CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA if medically significant hypertension cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.Infusion-Related ReactionsPrior to the institution of premedication recommendations across clinical trials of CYRAMZA, infusion-related reactions (IRRs) occurred in 6 out of 37 patients (16%), including two severe events. The majority of IRRs across trials occurred during or following a first or second CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. Monitor patients during the infusion for signs and symptoms of IRRs in a setting with available resuscitation equipment. Immediately and permanently discontinue CYRAMZA for Grade 3 or 4 IRRs.Gastrointestinal PerforationsCYRAMZA is an antiangiogenic therapy that can increase the risk of gastrointestinal perforation, a potentially fatal event. Four of 570 patients (0.7%) who received CYRAMZA as a single agent in clinical trials experienced gastrointestinal perforation. In Study 2, the incidence of gastrointestinal perforations was also increased in patients that received CYRAMZA plus paclitaxel (1.2%) as compared to patients receiving placebo plus paclitaxel (0.3%). In Study 3, the incidence of gastrointestinal perforation was 1% for CYRAMZA plus docetaxel and 0.3% for placebo plus docetaxel. In Study 4, the incidence of gastrointestinal perforation was 1.7% for CYRAMZA plus FOLFIRI and 0.6% for placebo plus FOLFIRI. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.Impaired Wound HealingImpaired wound healing can occur with antibodies inhibiting the VEGF pathway. CYRAMZA has not been studied in patients with serious or non-healing wounds. CYRAMZA, as an antiangiogenic therapy, has the

potential to adversely affect wound healing. Withhold CYRAMZA prior to surgery. Resume following the surgical intervention based on clinical judgment of adequate wound healing. If a patient develops wound healing complications during therapy, discontinue CYRAMZA until the wound is fully healed.Clinical Deterioration in Patients with Child-Pugh B or C CirrhosisClinical deterioration, manifested by new onset or worsening encephalopathy, ascites, or hepatorenal syndrome was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis only if the potential benefits of treatment are judged to outweigh the risks of clinical deterioration.Reversible Posterior Leukoencephalopathy Syndrome (RPLS)RPLS has been reported with a rate of <0.1% in clinical studies with CYRAMZA. Confirm the diagnosis of RPLS with MRI and discontinue CYRAMZA in patients who develop RPLS. Symptoms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death.Proteinuria Including Nephrotic Syndrome In Study 4, severe proteinuria occurred more frequently in patients treated with CYRAMZA plus FOLFIRI compared to patients receiving placebo plus FOLFIRI. Severe proteinuria was reported in 3% of patients treated with CYRAMZA plus FOLFIRI (including 3 cases [0.6%] of nephrotic syndrome) compared to 0.2% of patients treated with placebo plus FOLFIRI. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio for the development of worsening of proteinuria during CYRAMZA therapy. Withhold CYRAMZA for urine protein levels that are 2 or more grams over 24 hours. Reinitiate CYRAMZA at a reduced dose once the urine protein level returns to less than 2 grams over 24 hours. Permanently discontinue CYRAMZA for urine protein levels greater than 3 grams over 24 hours or in the setting of nephrotic syndrome.Thyroid Dysfunction Monitor thyroid function during treatment with CYRAMZA. In Study 4, the incidence of hypothyroidism reported as an adverse event was 2.6% in the CYRAMZA plus FOLFIRI treated patients and 0.9% in the placebo plus FOLFIRI treated patients.Embryofetal Toxicity Based on its mechanism of action, CYRAMZA can cause fetal harm when administered to pregnant women. Animal models link angiogenesis, VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CYRAMZA and for at 3 least months after the last dose of CYRAMZA.

ADVERSE REACTIONSClinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.CYRAMZA Administered in Combination with DocetaxelStudy 3 was a multinational, randomized, double-blind study conducted in patients with NSCLC with disease progression on or after one platinum-based therapy for locally advanced or metastatic disease. Patients received either CYRAMZA 10 mg/kg intravenously plus docetaxel 75 mg/m2 intravenously every 3 weeks or placebo plus docetaxel 75 mg/m2 intravenously every 3 weeks. Due to an increased incidence of neutropenia and febrile neutropenia in patients enrolled in East Asian sites, Study 3 was amended and 24 patients (11 CYRAMZA plus docetaxel, 13 placebo plus docetaxel) at East Asian sites received a starting dose of docetaxel at 60 mg/m2 every 3 weeks. Study 3 excluded patients with an ECOG PS of 2 or greater, bilirubin greater than the upper limit of normal (ULN), uncontrolled hypertension, major surgery within 28 days, radiographic evidence of major airway or blood vessel invasion by cancer, radiographic evidence of intra-tumor cavitation, or gross hemoptysis within the preceding 2 months, and patients receiving therapeutic anticoagulation or chronic anti-platelet therapy other than once daily aspirin. The study also excluded patients whose only prior treatment for advanced NSCLC was a tyrosine kinase (epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK]) inhibitor. The data described below reflect exposure to CYRAMZA plus docetaxel in 627 patients in Study 3. Demographics and baseline characteristics were similar between treatment arms. Median age was 62 years; 67% of patients were men; 84% were White and 12% were Asian; 33% had ECOG PS 0; 74% had non-squamous histology and 25% had squamous histology. Patients received a median of 4.5 doses of CYRAMZA; the median duration of exposure was 3.5 months, and 195 (31% of 627) patients received CYRAMZA for at least six months. In Study 3, the most common adverse reactions (all grades) observed in CYRAMZA plus docetaxel-treated patients at a rate of ≥30% and ≥2% higher than placebo plus docetaxel were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation. Treatment discontinuation due to adverse reactions occurred more frequently in CYRAMZA plus docetaxel-treated patients (9%) than in placebo plus docetaxel-treated patients (5%). The most common adverse events leading to treatment discontinuation of CYRAMZA were infusion-related reaction (0.5%) and epistaxis (0.3%). For patients with non-squamous histology, the overall incidence of pulmonary hemorrhage was 7% and the incidence of ≥Grade 3 pulmonary hemorrhage was 1% for CYRAMZA plus docetaxel compared to 6% overall incidence and 1% for ≥Grade 3 pulmonary hemorrhage for placebo plus docetaxel. For patients with squamous histology, the overall incidence of pulmonary hemorrhage was 10% and the incidence of ≥Grade 3 pulmonary hemorrhage was 2% for CYRAMZA plus docetaxel compared to 12% overall incidence and 2% for ≥Grade 3 pulmonary hemorrhage for placebo plus docetaxel. The most common serious adverse events with CYRAMZA plus docetaxel were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%). The use of granulocyte colony-stimulating factors was 42% in CYRAMZA plus docetaxel-treated patients versus 37% in patients who received placebo plus docetaxel. In patients ≥65 years, there were 18 (8%) deaths on treatment or within 30 days of discontinuation for CYRAMZA plus docetaxel and 9 (4%) deaths for placebo plus docetaxel. In patients <65 years, there were 13 (3%) deaths on treatment or within 30 days of discontinuation for CYRAMZA plus docetaxel and 26 (6%) deaths for placebo plus docetaxel. Table 4 provides the frequency and severity of adverse reactions in Study 3.

Table 4: Adverse Reactions Occurring at Incidence Rate ≥5% and a ≥2% Difference Between Arms in Patients Receiving CYRAMZA in Study 3

Adverse Reactions (MedDRA)System Organ Class

CYRAMZA plus docetaxel(N=627)

Placebo plus docetaxel(N=618)

All Grades(Frequency %)

Grade 3-4(Frequency %)

All Grades(Frequency %)

Grade 3-4(Frequency %)

Blood and Lymphatic System Disorders

Febrile neutropenia 16 16 10 10

Neutropenia 55 49 46 40

Thrombocytopenia 13 3 5 <1

Gastrointestinal Disorders

Stomatitis/Mucosal inflammation 37 7 19 2

24 | Oncologistics

Eye on ION

The Metamorphosis of a Community Oncology PracticeA story of woe (and wow) half a century in the making.Most narratives referring to a metamorphosis of a community practice end with the practice evolving into a health system or valiantly maintaining their independence through thoughtful design. This is not one of those stories. This is the chronicle of how one community oncology practice — over the course of roughly five decades — engaged with patients but disengaged with industry trends, picked the wrong side in a war of attrition, marched naively into the mouth of a giant and, subsequently, lost a few limbs during its exit. But this is not a story of its undoing. It’s a story of its rebuilding … through new partnerships, new technologies and a renewed commitment to its founding principles.

Dr. Tracey Weisberg, president and lead physician at New England Cancer Specialists, helps to tell it. As she says, “We have a voice. As community oncologists, we need to use our voice to be present for both our patients and fellow physicians. It’s in the preservation of these relationships that we will find what we need to survive.”

Late 1970s and 80s

“Now they had an actual treatment room.

Patients were no longer being seen in a

bedroom that had been made to look like a

therapy room.”

–Dr. Weisberg

The practice has a revelation: One doctor cannot do it all. Two partners are brought into the fold to help. Also, the decision to move out of the residential home and into a professional office is made.

Maine Center for Cancer Medicine (later to be renamed New England Cancer Specialists) is made official, complete with actual treatment rooms and a receptionist.

The 1960s

“They knew everyone’s name. It was all about

high-touch care. There were no oncology

boards, no electronic health records (EHR).

Handwritten records were kept in the barn.”

–Dr. Weisberg

Picture a large, colonial-style home set on the eastern promenade of Portland, Maine. A stroll around the grounds reveals a backhouse of almost equal proportions to the main house. Inside, cancer patients wait to see Dr. Ronald Carroll, Maine’s first medical oncologist. This is where New England Cancer Specialists got its start, and where our story begins.

With little more than a stethoscope, pen and paper, one doctor does it all. Dr. Carroll sees patients in his residential medical center, he’s on call 24/7, he makes home visits and attends deaths.

“We have a voice. As community oncologists, we need to use our voice to

be present for both our patients and fellow physicians.”

25 | Oncologistics

Early to mid-1990s

“We were so engaged with the hospital. We

performed rounds at the hospital twice a

day and went to every staff meeting. Hospital

dinners, cocktail hours and holiday parties …

everyone went.”

–Dr. Weisberg

As cancer diagnoses and treatments grow, so too does the practice. It opens a satellite office in Brunswick, Maine, and launches rural clinics. More doctors are added to the team, including the practice’s first female oncologist, Dr. Weisberg. The practice also begins to conduct clinical research. No one is discussing money, just growth.

In addition to performing rounds at the hospital twice a day and attending all the hospital’s meetings and events, the practice has access to the hospital’s doctor’s lounge (land of the free coffee and doughnuts). It is here the oncologists find where their next consult will come from.

Beyond the doctor’s lounge, rising hospital admissions caused by 5-fluorouracil (5-FU) infusions and negative reactions to chemotherapies are keeping the practice staff working around the clock.

Late 1990s

“We wanted to be the hospital’s right-hand

man. We shared our research results and

helped them open multi-disciplinary clinics,

including the creation of a Breast Cancer Clinic.

We were the only ones, however, paying rent.”

–Dr. Weisberg

In addition to hiring its first physician assistant, the practice adopts its first EHR system. While some members of the staff are certain of the value medical data will have in the future, the physicians aren’t sure how to collect it. This later proves detrimental.

The practice feels they are a valued collaborator with the hospital. When the opportunity to move into a hospital-owned building presents itself, it jumps at it.

Still, no one is discussing the financial viability of the practice. Does anyone know?

2006

“Oncology was changing all around us.

Sequestration and the Sustainable Growth Rate

(SGR) were a yearly concern. Hospitals were

buying practices. We heard about 340B and

ACOs … but we thought other people were

going to have to make the hard changes. Then

they’d see how bad it was and we wouldn’t

ever have to do anything.”

–Dr. Weisberg

The practice hires a CEO with an MBA to help run the business side of things. It incorporates genetics into the practice and more physicians are added to the team. The practice forms a joint venture with the hospital to open a fourth site in Sanford, Maine. And though it vexes the partners, they must migrate to a new EHR system.

Disenchanting discourse ensues between the hospital and practice over how to handle drug replacements and the treatment of free-care patients. The doughnuts and coffee in the hospital’s doctor’s lounge are no longer free, nor is parking for the practice. Soon, the hospital closes the lounge completely.

2009 to 2011

“We almost die. The partners are not keeping

any eye on the business.”

–Dr. Weisberg

The partners cannot figure out how to get paid for genetic testing. They question the expense of clinical research. Spend on drugs is escalating. To add insult to injury, the CEO with the MBA demonstrates a desire for the practice to be absorbed by the hospital.

The hospital census is getting higher. And while its residents do less, the practice does more. Its oncologists are often up all night on call. The practice has no access to the hospital’s hospitalists.

Oncologistics | 26

Meanwhile, the insurers inform the practice that they may be the least expensive cancer care in the entire state. But because there are no useful data in the EHR, the partners cannot substantiate such a claim.

In an ironic twist, the practice must once again migrate to another EHR.

The CEO and the practice go their separate ways.

2012

“At this point the practice is in what I refer

to as the winter of its business cycle. There’s

only two things one can do in winter: Die or

innovate.”

–Dr. Weisberg

The practice creates a formal leadership team and hires a new CEO, Steve D’Amato. He’s a risk taker and understands no practice will survive without moving forward.

Step one in the new agenda: Orchestrate a plan to ensure individualized care while expanding the practice. This will demand operational insight and efficiency. The decision is made to partner with a third-party oncology supply company.

Step two: Establish an identity apart from the hospital. This begins with a name change. The practice is reborn as it remains today: New England Cancer Specialists.

With a renewed commitment to its patients and employees, the practice works to create a brand.

2013

“It was like a Cold War. We were asked to

go into consultations with the hospital to

discuss alignment. They did not like our new

business plan.”

–Dr. Weisberg

The practice is now active in ASCO and ACCC. It starts to advertise and tell its story. This puts even more tension between the hospital and practice.

New England Cancer Specialists is selected to be a COME HOME practice. While this results in its having to refine its EHR, the partners now know how to collect data — and its value. Through COME HOME, it develops relationships with oncology organizations that share EHR, best practices, approaches to team-based care, paths to enhanced access and financial support.

The insurers are asking the practice to partner with them on payment reform projects. Physicians align and engage in patient pathway committees. Although fiercely independent, the practice is no longer alone.

“If you make a mistake, you’ll figure

it out. You’ll find another solution. But

to just sit there, that will lead us to

certain death.”

27 | Oncologistics

Oncologistics | 29

Today

“We received our oncology medical home accreditation in 2015. And boy did it deliver. We have

fewer ER visits, fewer ambulatory-care sensitive hospitalizations. Our readmission rate is lower.”

–Dr. Weisberg

Through captured data, New England Cancer Specialists realizes it is in fact the least expensive cancer care in Maine. In colon cancer, it is almost $40,000 less per patient. In breast cancer, about $20,000 less. In prostate cancer, $10,000 less.

“It’s not just the drugs,” says Dr. Weisberg. “It’s that our doctors are thinking harder. They’re not admitting patients to the hospital. They’re using more thoughtful radiation techniques. They’re going to lower site cost of care for imaging and other services.”

While it wasn’t the easiest path (or the shortest), the practice has managed to evolve into what it wanted to be 50 years ago: A place of personalized, high-quality care embedded in advanced technologies and cancer treatments. Equally important, it now has a voice and a story to tell — one that might encourage other practices to engage, transform and accept risk. Because, as illustrated by New England Cancer Specialists, staying the same is not an option for survival. “If you don’t execute you die,” says Dr. Weisberg. “If you make a mistake, you’ll figure it out. You’ll find another solution. But to just sit there, that will lead us to certain death.”

To learn about Dr. Weisberg or New England Cancer Specialists, visit NewEnglandCancerSpecialists.org.

Oncologistics | 28

Myriad Genetics Inc. Forms Relationship with ION Solutions to Deliver Quality Hereditary Cancer Tests and Services

ION Solutions and Myriad Genetics, Inc. (NASDAQ: MYGN), a global leader in personalized medicine, have entered into a relationship to deliver quality hereditary cancer test results and services to ION member practices. Through this relationship, Myriad and ION will work together to enhance the operational and clinical value associated with hereditary cancer testing. Myriad will be ION’s preferred partner for hereditary cancer testing focused on bringing specialized tests and services to meet the specific needs of community oncology practices. This partnership will advance the organizations’ shared goals of providing accurate and comprehensive hereditary cancer test results and service to community oncologists and their patients.

“Myriad has demonstrated its commitment to quality with its significant investments in research, laboratory processes, variant interpretation and exceptional customer service,” said Mark Santos, RPh, president of ION GPO. “This relationship supports ION Solutions in making important genetic tests available to our members in a way that will help inform treatment decisions and build patient care plans in the context of specific practice processes and objectives.”

“ION Solutions is the industry leader in bringing effective business and clinical solutions to the largest segment of community oncology practices in the nation,” said Alexander Ford, president of Myriad Genetic Laboratories, Inc. “Our focus as a company is on providing accurate, affordable and clinically significant genetic test results to providers and the patients they care for. We believe we share this commitment with ION Solutions and their members, and that through this partnership, the largest, most innovative private practices in the country will gain enhanced access to our services.”

Understanding the Merit-based Incentive Payment System (MIPS)

The Merit-based Incentive Payment System (MIPS) is a new payment model that provides eligible clinicians financial adjustments based on quality, outcomes and efficiency. MIPS consolidates the existing quality reporting systems—Physician Quality Reporting System (PQRS), the Value-based Payment Modifier and the EHR Incentive Program (Meaningful Use)—into one scoring system that is based on four categories: Quality, Advancing Care Information, Improvement Activities and Cost.

Quality

CMS has taken the current measures from PQRS and VBM programs and used them to create the Quality category. In the 2017 performance year, which is the 2019 payment year, Quality measures will count for 60 percent of your total MIPS score.

Clinicians will have to report six measures from approximately 200 quality measures, including one cross-cutting patient-facing measure and one outcome measure.

In addition, clinicians will be scored on two – three population quality measures. These measures will be claim based and the measures you are scored on will be determined by the number of eligible cases for each clinician and the reporting option your practice chooses.

Advancing Care Information

Under Advancing Care Information, which will account for 25 percent of the total calculation in the first year, clinicians will report on key measures of interoperability and information exchange. Under this measure the reporting period is for a full calendar year, not a 90-day period as several other measures.

What’s News at ION

30 | Oncologistics

Shrinking margins have pushed independent specialty practices

to place even greater focus on operational efficiency. In response,

successful practices have turned to their GPO and distribution

pa r t ne r for c u s tom i z ed i nve ntor y m a n age me nt , a s we l l a s

integrated technologies and business consulting, to increase time

with patients. Improving cash f low takes a streamlined workflow.

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SPECIALTY DISTRIBUTION \ GPO SERVICES \ TECHNOLOGY AND BUSINESS CONSULTING \ SPECIALTY PHARMACY

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Practices need to ensure that their EHR can acquire all the information that is required and make those adjustments before year end in order to achieve the points. One important aspect of the program is that practices must perform a security risk analysis. Those who do not will be ineligible for any points in this performance measure as it is a core measure.

The six performance measures under this category for the Modified Stage 2 in 2017 include:

■ Patient Access

■ View, Download or Transmit Information

■ Patient Education

■ Secure Messaging

■ Health Information Exchange

■ Medication Reconciliation

Improvement Activities

The Improvement Activities category, 15 percent of your score, emphasizes the completion of practice improvement activities. Practices will be asked to complete at least one Improvement Activity from the 90-plus available.

The categories (and possible examples) that will be included under IA are:

■ Expanded Practice Access - the collection of patient satisfaction data

■ Population Management - including items like reconciling medications or providing medication management

■ Care Coordination - developing pathways to community-based resources like chronic health management groups

■ Beneficiary Engagement – providing specific self-management materials

■ Patient Safety and Practice Assessment – completion of the AMA’s STEPS Forward program

■ Participation in an APM, including a medical home model

■ Achieving Health Equity – seeing new and follow-up Medicaid patients in a timely matter

■ Emergency Preparedness and Response – participation in a Community Emergency Responder Team for at least six months

■ Integrated Behavior and Mental Health – engagement in prevention or treatment interventions for tobacco use or cessation

Cost

The Centers for Medicare & Medicaid Services (CMS) will specify and calculate cost measures for this category in 2017.

For more information or help implementing MIPS in your practice, contact ION Solutions’ Value-based Care Management Services at insidesales@iononline.com or 877-570-8721 x2.

What’s News at ION

Learn more by viewing one of our MIPS webinars. Go to www.iononline.com, click on Meetings and Webcasts and go to the Webcast Archives.

We Support the Health of your PracticeWith the Same Dedication that You Support Your Patients

Your number one priority is the health of your patients. With the changing healthcare landscape, our number one priority is the business health of your practice.

Dedicated exclusively to the viability of community oncology, ION Solutions provides contracting, technology, education and advocacy support that ensures you have the tools to run your practice both ef�ciently and effectively. With the practice support of ION Solutions, you can navigate this changing environment and focus on providing quality care for your patients.

To learn how ION Solutions enables community oncology practices to improve operational efficiency, financial performance and quality of care, contact your Strategic Account Manager or visit IONonline.com.

To experience ION Solutions advocacy support, visit ourcommunitycounts.org.