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A Journal Article Review: “Enzalutamide in Metastatic Prostate Cancer before Chemotherapy”Beer T.M., Armstrong A.J., Rathkopf D.E., et al. N Engl J Med 2014; 371:424-433

Jenna Gianninoto, PharmD, CSPAvella Specialty Pharmacy

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Disclaimer

• The information is for educational purposes only, and is not

intended to substitute for the medical judgment of the healthcare

provider. Recommendations for use of any particular therapeutic

agents or methods are based upon the best available scientific

evidence and clinical guidelines. Reference in this activity to any

specific commercial products, process, service, manufacturer, or

company does not constitute its endorsement or

recommendation. Off-label use of therapeutic agents will be

discussed.

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Disclosure

• Dr. Gianninoto serves as a compensated employee of Avella Specialty Pharmacy.

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Pharmacologic Treatment of Prostate Cancer

• LHRH agonists

• LHRH antagonists

• Chemotherapy

• Anti-androgens

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Abiraterone • MOA

– Selectively and irreversibly inhibits CYP17

– Inhibits the formation of the testosterone precursors

• Indication – Treatment of metastatic

castration-resistant prostate cancer in combination with prednisone

Zytiga [package insert] Janssen Biotech Inc.

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Abiraterone

• Administration and dosage – 1000mg once daily

• Common ADE– Joint swelling, hypokalemia,

edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, and upper respiratory tract infection.

• “Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy”– Improved radiographic PFS– Improved overall survival – Safety profile similar to

what was previously reported

Zytiga [package insert] Janssen Biotech Inc.Ryan C.J., Smith M.R., de Bono J.S., et al. N Engl J Med 2013; 368:138-148

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Enzalutamide• MOA

– Androgen receptor inhibitor – Competitively inhibits

androgen binding to receptors and inhibits androgen receptor nuclear translocation and interaction with DNA

• Indication – Treatment of patients with

metastatic castration-resistant prostate cancer who have previously received docetaxel

Xtandi [package insert] Astellas Pharma Inc.

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Enzalutamide

• Dosage and administration– 160mg (four 40mg capsules) by mouth once daily– Administered with or without food – No initial dosage adjustments for mild to moderate

renal or hepatic impairment is necessary – Store at room temperature

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Enzalutamide

• Common ADE– Asthenic conditions– Anxiety– Diarrhea– Dizziness– Hot Flush– Hypertension – Insomnia– Musculoskeletal pain– Peripheral edema– Respiratory tract

infection

• Warnings– Seizure

• In clinical trials, 0.9% of patients treated with enzalutamide experienced a seizure.

– Fertility impairment • Male fertility may be

impaired with treatment

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Enzalutamide

• Drug-Drug Interactions – Metabolized via CYP 3A4 and 2C8

• 3A4 – Strong/moderate inducers: carbamazepine,

phenytoin– Strong/moderate inhibitors: itraconazole

• 2C8 – Strong/moderate inducers: rifampin– Strong/moderate inhibitors: gemfibrozil

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“Enzalutamide in Metastatic Prostate Cancer before Chemotherapy”

Beer T.M., Armstrong A.J., Rathkopf D.E., et al. N Engl J Med 2014; 371:424-433

• Study Design– Double-blind, randomized, placebo controlled– Phase three trial– From September 2010 to September 2012

1717 patients enrolled in the study– 207 sites globally

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Primary and Secondary Endpoints

• Co-primary endpoints– Radiographic progression-free survival– Overall survival

• Secondary endpoints– Time until initiation of cytotoxic chemotherapy– Time until the first skeletal-related event– Best overall soft-tissue response– Time until PSA progression– Decline in PSA level of 50% or more from baseline

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Statistical Analysis

• Goal for enrollment was ~1680 patients

• Co-primary endpoints analyzed in the intention-to-treat population – Total type I error rate of 0.05

• Secondary endpoints analyzed using Holm’s step-down procedure

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Participants

• Eligibility criteria – Adenocarcinoma of the prostate with documented

metastases – PSA and/or radiographic progression in bone or soft

tissue– Prior therapy – Eastern Cooperative Oncology Group performance status– Asymptomatic or mildly symptomatic disease

• Exclusion criteria – Seizure

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Results

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Clinical Significance

• Option for patients with metastatic prostate cancer prior to chemotherapy use

• Safety profile similar to previously reported

• Significantly delayed – Radiographic disease progression or death– The need for cytotoxic chemotherapy– Deterioration in quality of life and significantly

improved overall survival

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Specialty versus Retail

Retail Specialty

Patient Contact Reactive Proactive

Drug Availability Limited Carried in stock

Clinical support Limited knowledge about lots of drugs Specialized knowledge

Availability of clinical staff Regular hours 24/7

Dispensing vs. patient care Low patient contact High Touch

Adherence/Persistence Tools Limited to none Numerous

Billing Multiple challenges Split Billing

Financial Assistance/PA’s Limited to none Core service

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The Path of a Specialty Prescription

Retail Rx

Specialty Rx

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Jenna Gianninoto, PharmD, CSP

jenna.gianninoto@avella.com

(877)792-7684 ext.3819