Give your patients with intermediate/poor-risk advanced or metastatic RCC a chance to start with the power of OPDIVO® + YERVOY®1

399 372 348 318 300425 241 119 2332 44OPDIVO +YERVOY

387 352 315 253 225422 179 89 300288 34sunitinib

Subjects at risk Time since randomization (months)

Prob

abili

ty o

f sur

viva

l

3 6 9 15 1800.00.1

0.2

0.3

0.5

0.4

0.6

0.7

0.8

0.9

1.0

21 27 30 3312 24

37%reduction in

instantaneousrisk of death

HR 0.63(99.8% CI: 0.44, 0.89)

p<0.0001

Median OSNot Estimable

25.9months

DEMONSTRATEDSUPERIOR OS VS.

SUNITINIB

Adapted from Product Monograph1*

OPDIVO + YERVOY(n=425)

PR: 32.2%(n=137)

CR: 9.4%(n=40)

ORR: 41.6%(95% CI: 36.9, 46.5)

0

10

20

30

40

50

Con

firm

ed o

bjec

tive

resp

onse

rate

(%)

sunitinib(n=422)

ORR: 26.5%(95% CI: 22.4, 31.0)

PR: 25.4%(n=107)

CR: 1.2%(n=5)

DEMONSTRATEDSUPERIOR

VS. SUNITINIBORR

p<0.0001

Adapted from Product Monograph1*

Among responders, the mDOR for OPDIVO + YERVOY has not yet been reached: NE (95% CI: 21,8, NE) vs. 18.2 months (95% CI: 14.8, NE) with sunitinib1

The trial did not demonstrate a statistically significant improvement in PFS: 11.6 months with OPDIVO + YERVOY vs. 8.4 with sunitinib; HR=0.82 (99.1% CI: 0.64, 1.05; p=0.0331)1

Generally well-tolerated safety profile The most frequent serious adverse reactions reported in at least 1% of patients were diarrhea (26.5%), pneumonitis (6.2%), hypophysitis (4.0%), adrenal insufficiency (5.3%), colitis (3.7%), hyponatremia (4.4%), increased ALT (41%), pyrexia (14.4%) and nausea (19.9%)1

Grade 3–4 adverse reactions: 46% with OPDIVO + YERVOY vs. 63% with sunitinib1

ORR: Objective response rate; CI: Confidence interval; CR: Complete response; PR: Partial response; mDOR: median duration of response; NE: Not estimable; OS: Overall survival; HR: Hazard ratio; PFS: Progression-free survival; ALT: Alanine aminotransferase; KCRNC: Kidney Cancer Research Network of Canada; VEGF: Vascular endothelial growth factor

* A randomized (1:1), open-label study in patients with previously untreated advanced or metastatic RCC. Patients were stratified by International Metastatic RCC Database Consortium (IMDC) prognostic score and region. The primary efficacy population included intermediate/poor risk patients with at least 1 or more of 6 prognostic risk factors as per the IMDC criteria. Patients were randomized to OPDIVO 3 mg/kg plus ipilimumab 1 mg/kg (n=425) administered intravenously every 3 weeks for 4 doses followed by OPDIVO monotherapy 3 mg/kg every two weeks (n=425) or to sunitinib (n=422) administered orally 50 mg daily for 4 weeks followed by 2 weeks off, every cycle. OS was assessed by an independent radiologic review committee.

OPDIVO and YERVOY and the OPDIVO and YERVOY logos are registered trademarks of Bristol-Myers Squibb Company used under license by Bristol-Myers Squibb Canada Co. ACCESS TO HOPE is a registered trademark of Bristol-Myers Squibb Company used under license by Bristol-Myers Squibb Canada Co.

Nivolumab, in combination with ipilimumab, is recommended by the KCRNC, as a first-line therapy option in intermediate/poor-risk advanced clear-cell RCC.2

Setting Patients Preferred therapy Options

Untreated

Favorable-risk (IMDC)* axitinib + pembrolizumab‡

sunitinibpazopanib

axitinib + avelumab†‡

High-dose IL-2§

Active surveillance

Intermediate/ poor-risk (IMDC)

ipilimumab + nivolumabaxitinib + pembrolizumab‡

sunitinibpazopanib

axitinib + avelumab†‡

cabozantinibActive surveillance

Second-line and beyond¶

Prior immune checkpoint inhibitor

cabozantinib**axitinib**

sunitinibpazopanib

lenvatinib + everolimus**

Prior VEGF nivolumabcabozantinib

lenvatinib + everolimuseverolimus

axitinib

Prior VEGF and immune checkpoint inhibitor cabozantinib

sunitinibpazopanibaxitinib†

lenvatinib + everolimuseverolimus

KCRNC: Selected therapeutic options for advanced clear-cell RCC2

Adapted from Hotte SJ, et al.2

* Nivolumab in combination with ipilimumab is not indicated for the treatment of clear-cell RCC in favorable-risk patients.

† Not yet approved in Canada‡ Awaiting mature overall survival data§ Not randomized controlled trial¶ If not used prior** Approved after 1 prior VEGF therapy only

Please refer to the Management of advanced kidney cancer: KCRNC consensus update 2019 statement for complete recommendations: http://dx.doi.org/10.5489/cuaj.6256

OPDIVO (nivolumab), in combination with ipilimumab, is indicated for the treatment of adult patients with intermediate/poor-risk advanced or metastatic renal cell carcinoma (RCC).

OPDIVO, as monotherapy, is indicated for the treatment of adult patients with advanced or metastatic renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

YERVOY, in combination with OPDIVO (nivolumab), is indicated for the treatment of adult patients with intermediate/poor-risk advanced or metastatic RCC.

Clinical use:Efficacy and safety not established in pediatric patients.

Most serious warnings and precautions:Severe/fatal immune-mediated adverse reactions (imARs): OPDIVO as monotherapy or in combination with YERVOY (ipilimumab) can cause severe and fatal immune-mediated adverse reactions, including pneumonitis, interstitial lung disease, encephalitis, myocarditis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and autoimmune hemolytic anemia. Immune-mediated adverse reactions may involve any organ system. Onset may occur during treatment or months after the last dose. Early diagnosis and appropriate management are essential to minimize potential life-threatening complications. Monitor patients for signs and symptoms of imARs and appropriately manage with treatment modifications. Permanently discontinue for any severe imARs that recur and for any life-threatening imARs.Administration: Administer OPDIVO under the supervision of physicians experienced in the treatment of cancer. Allogeneic hematopoietic stem cell transplantation (HSCT): Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Preliminary results from the follow-up of patients undergoing allogeneic HSCT after previous exposure to nivolumab showed a higher than expected number of cases of acute graft-versus-host disease (GVHD) and transplant related mortality. Complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic venoocclusive disease (VOD), and other immune-mediated adverse reactions, and intervene promptly. Multiple myeloma: Increased mortality in patients with multiple myeloma [not an approved indication] when OPDIVO is added to a thalidomide analogue and dexamethasone. Treatment of patients with multiple myeloma with a PD-1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Other relevant warnings and precautions: • Severe cases of these imARs have been observed, including

fatal cases. Monitor patients for signs and symptoms of the following imARs:- Endocrinopathies, including hypothyroidism, hyperthyroidism,

hypoparathyroidism, adrenal insufficiency, hypophysitis, diabetes mellitus, and diabetic ketoacidosis

- Diarrhea, additional symptoms of colitis, and cytomegalovirus (CMV) infection/reactivation

- Hepatotoxicity, including hepatitis- Nephrotoxicity, including nephritis and renal failure- Rash- Haemophagocytic lymphohistiocytosis (HLH)- Other imARs, including myotoxicity and solid organ transplant

rejection and rapid-onset and severe graft-versus-host disease (GVHD)

• Infusion reaction• Patients on controlled sodium diet• Pregnancy and nursing women• Has not been studied in patients with moderate or severe hepatic

or severe renal impairment

For more information:Please consult the OPDIVO Product Monograph at https://www.bmscanada.ca/en/pm/OPDIVO_EN_PM.pdf for important information relating to adverse reactions, drug interactions, and dosing, which have not been discussed in this piece.The Product Monograph is also available by calling us at: 1-866-463-6267.

Pr

Clinical use:Efficacy and safety not established in pediatric patients.

Contraindication:In patients with active, life-threatening autoimmune disease, or with organ transplantation graft where further immune activation is potentially imminently life threatening.

Most serious warnings and precautions:Administered under supervision of physicians experienced in the treatment of cancer. Severe/fatal immune-mediated adverse reactions (imARs): including enterocolitis, intestinal perforation, hepatitis, dermatitis (incl. toxic epidermal necrolysis), neuropathy, endocrinopathy, pneumonitis, myocarditis, encephalitis, myasthenia gravis, and other organ system toxicities. Most occurred during the induction period; onset months after the last dose has been reported. Early diagnosis and appropriate management are essential to minimize life-threatening complications. Monitor closely; clinical chemistries should be evaluated at baseline and before each dose. Diarrhea, increased stool frequency, bloody stool, liver function test elevations, rash, and endocrinopathies must be considered immune-mediated and YERVOY-related, unless an alternate etiology has been identified. Discontinue permanently in case of severe imARs; systemic high-dose corticosteroid +/- additional immunosuppressive therapy may be required.Other relevant warnings and precautions:• Patients who have had a severe or life-threatening skin adverse

reaction on a prior cancer immune stimulatory therapy• Monitor for signs/symptoms of:

- Enterocolitis and bowel perforation- Hepatotoxicity before each dose and monitor liver function tests- Dermatitis- Motor or sensory neuropathy- Hypophysitis, adrenal insufficiency, hyper- or hypothyroidism

• Other imARs including ocular events• Vogt-Koyanagi-Harada syndrome • Infusion reaction• Patients on immunosuppressive therapy for life-threatening

disease or condition• Patients on controlled sodium diet• Concurrent administration with vemurafenib• Patient counseling information: imARs and fatigue• Hepatic impairment• Renal impairment• Pregnancy and nursing women• Close monitoring required: liver function tests, thyroid function

test, electrolytes, any signs of imARs.• When using YERVOY in combination with OPDIVO (nivolumab),

consult the Product Monograph for OPDIVO (nivolumab) for further information on this drug.

For more information:Please consult the YERVOY Product Monograph at https://www.bms.com/assets/bms/ca/documents/productmonograph/YERVOY_EN_PM.pdf for important information relating to adverse reactions, management of imARs, drug interactions, and dosing information, which have not been discussed in this piece.The Product Monograph is also available by calling us at: 1-866-463-6267.

OPDIVO and YERVOY and the OPDIVO and YERVOY logos are registered trademarks of Bristol-Myers Squibb Company used under license by Bristol-Myers Squibb Canada Co. ACCESS TO HOPE is a registered trademark of Bristol-Myers Squibb Company used under license by Bristol-Myers Squibb Canada Co.

References:1. OPDIVO Product Monograph. Bristol-Myers Squibb Canada Co. 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Kidney Cancer. Version 2.2019 – September 17, 2018. 3. YERVOY Product Monograph. Bristol-Myers Squibb Canada Co.

Give your patients with intermediate/poor-risk advanced or metastatic RCC a chance to start with the power of OPDIVO® + YERVOY®1