In the 1L treatment of patients with intermediate or poor risk advanced renal cell carcinoma1,2
DURABILITY WITH OPDIVO + YERVOY:
The only I-O combination with a chance for durable survival and durable response data at 5 years*†
*Based on results from an extended follow-up
analysis at a minimum of 60 months.3
†In a phase 3 trial.3
Checkmate 214 Primary Analysis Median follow-up time of 25.2 months
In the primary analysis of Checkmate 214 (median follow-up time of 25.2 months):
- Median OS not yet reached (95% CI: 28.2–NE) for OPDIVO + YERVOY vs 25.9 months (95% CI: 22.1–NE) for sunitinib; HR=0.63 (99.8% CI: 0.44–0.89); P<0.00011,4
- Confirmed ORR‡: 41.6% (n=177/425) (95% CI: 36.9–46.5) for OPDIVO + YERVOY vs 26.5% (n=112/422) (95% CI: 22.4–31.0) for sunitinib (P<0.0001)1,4
- CR: 9.4% (n=40) for OPDIVO + YERVOY vs 1.2% (n=5) for sunitinib1,4
- PR: 32.2% (n=137) for OPDIVO + YERVOY vs 25.4% (n=107) for sunitinib1,4
- Among responders, median DOR was not evaluable (NE) (95% CI: 21.8–NE) for OPDIVO + YERVOY vs 18.2 months (95% CI: 14.8–NE) for sunitinib1,4
- Median PFS‡: 11.6 months (95% CI: 8.7–15.5) for OPDIVO + YERVOY vs 8.4 months (95% CI: 7.0–10.8) for sunitinib; HR=0.82 (99.1% CI: 0.64–1.05)1,4
- Per pre-specified analysis, progression-free survival did not meet statistical significance1,4
In the extended analysis of Checkmate 214 (minimum follow-up time of 60 months):
- mOS:
- The 60-month OS rate for OPDIVO + YERVOY was 43% vs 31% for sunitinib3
- mOS for OPDIVO + YERVOY was 47.0 months (95% CI: 35.4–57.4) vs 26.6 months (95% CI: 22.1–33.5)3 for sunitinib. HR=0.68 (95% CI: 0.58–0.81)3
- ORR‡:
- OPDIVO + YERVOY: ORR; 42.1% (n=179/425 [95% CI: 37.4–47.0]; CR: 11.3% [n=48]; PR: 30.8% [n=131])3,5
- Sunitinib: ORR: 26.8% (n=113/422 [95% CI: 22.6–31.3]; CR: 2.1% [n=9]; PR: 24.6% [n=104])3,5
- mDOR‡:
- Among responders, median DOR was not yet reached (95% CI: 50.9–NE) for OPDIVO + YERVOY vs 19.7 months (95% CI: 15.4–25.1) for sunitinib3,5
- HR=0.46 (95% CI: 0.31–0.66)3,5
‡PFS and ORR were assessed by an independent radiographic review committee per RECIST v1.1.1,3,4
Scroll to see additional information,
including primary and extended follow-up data below
Select Important Safety Information
Serious Adverse Reactions
- In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis.
Common Adverse Reactions
- In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%).
In the 60-month follow-up analysis, all-cause adverse events occurring in >15% of patients receiving OPDIVO + YERVOY and not previously included in the primary analysis include: upper respiratory tract infection (OPDIVO + YERVOY: 21.6% Grades 1-4; 0.4% Grades 3-4; sunitinib: 15.0% Grades 1-4)12
Please see additional Important Safety Information below and U.S. Full Prescribing Information for OPDIVO and YERVOY.
additional data.
Baseline Characteristics
Checkmate 214 baseline characteristics1,4,6
IMDC intermediate or poor risk patients
Characteristic | OPDIVO + YERVOY (n=425) | Sunitinib (n=422) |
---|---|---|
Median age, years4,5 ≥65 years, % | 62 38 8 | 61 39 7 |
Male, %4 | 74 | 71 |
IMDC prognostic score, %4 Intermediate (1–2) | 79 21 | 79 21 |
No. of sites with ≥1 target/non-target lesion, %4 1 | 21 79 | 20 80 |
Quantifiable tumor PD-L1 expression, %4 <1% | (n=384) 74 26 | (n=392) 71 29 |
Most common site of metastasis, %4 Lung | 69 45 22 21 | 70 51 23 21 |
Characteristic | OPDIVO + YERVOY (n=425) | Sunitinib (n=422) |
---|---|---|
Median age, years4,5 ≥65 years, % | 62 38 8 | 61 39 7 |
Male, %4 | 74 | 71 |
IMDC prognostic score, %4 Intermediate (1–2) | 79 21 | 79 21 |
No. of sites with ≥1 target/ 1 | 21 79 | 20 80 |
Quantifiable tumor PD-L1 expression, %4 <1% | (n=384) 74 26 | (n=392) 71 29 |
Most common site of metastasis, %4 Lung | 69 45 22 21 | 70 51 23 21 |
§Of evaluable patients (n=284/384).4
1L aRCC patients qualify as
intermediate or poor risk4,7-9||
||Based on large, retrospective, population-based studies.4, 7-9
IMDC Risk Factors
Up to 80% of 1L aRCC patients qualify as intermediate or poor risk8||
Intermediate or poor risk patients have ≥1 prognostic risk factor per the IMDC criteria8
||Based on large, retrospective, population-based studies.4
Overall Survival
In the 1L treatment of intermediate/poor risk aRCC
OPDIVO + YERVOY: A chance for durable survival at 5 years1,3,4,10
43% of patients were still alive at 5 years with OPDIVO + YERVOY vs 31% for sunitinib3¶
5-year minimum follow-up: OS in patients with intermediate/poor risk aRCC1,3,4,10#
The 60-month overall survival rate analysis was not pre-specified within the study protocol.10 In the primary analysis, the pre-specified 12-month overall survival rate was 80% (95% CI: 76–84) with OPDIVO + YERVOY vs 72% (95% CI: 67–76) with sunitinib. The median follow-up time was 25.2 months.4,11
mOS at primary analysis (median follow-up time of 25.2 months)1,4
- OPDIVO + YERVOY: Not yet reached (95% CI: 28.2–NE)1,4
- Sunitinib: 25.9 months (95% CI: 22.1–NE)1,4
- HR=0.63 (99.8% CI: 0.44–0.89); P<0.00011,4
mOS at extended follow-up (minimum follow-up time of 60 months)3
- OPDIVO + YERVOY: 47.0 months (95% CI: 35.4–57.4)3
- Sunitinib: 26.6 months (95% CI: 22.1–33.5)3
- HR=0.68 (95% CI: 0.58–0.81)3
¶In a phase 3 trial.3,4
#Performance status is based on IMDC prognostic score (0=favorable, 1-2=intermediate, 3+=poor).4
Progression-Free Survival
In the 1L treatment of intermediate/poor risk aRCC
Progression-free survival data at 5 years3**
5-year minimum follow-up: PFS in patients with intermediate/poor risk aRCC1,3,4,10
mPFS** at primary analysis (median follow-up time of 25.2 months)1,4
- OPDIVO + YERVOY: 11.6 months (95% CI: 8.7–15.5)1,4
- Sunitinib: 8.4 months (95% CI: 7.0–10.8)1,4
- HR=0.82 (99.1% CI: 0.64–1.05)1,4
- Per a pre-specified analysis, PFS did not meet statistical significance1,4
mPFS** at extended follow-up (minimum follow-up time of 60 months)3
- OPDIVO + YERVOY: 11.6 months (95% CI: 8.4–16.5)3
- Sunitinib: 8.3 months (95% CI: 7.0–10.4)3
- HR=0.73 (95% CI: 0.61–0.87)3
**In both the primary analysis and the extended follow-up analysis, PFS was assessed by an independent radiographic review committee per RECIST v1.1.1,3,4
Overall Response Rate
(DOR, CR)
In the 1L treatment of intermediate/poor risk aRCC
With OPDIVO + YERVOY, there was a 56% chance for responses to last 5 years1,3-5
ORR†† at primary analysis (median follow-up time of 25.2 months)1,4
- OPDIVO + YERVOY: ORR: 41.6% (n=177/425) (95% CI: 36.9–46.5%); CR: 9.4% (n=40); PR: 32.2% (n=137)1,4
- Sunitinib: ORR: 26.5% (n=112/422) (95% CI: 22.4–31.0); CR: 1.2% (n=5); PR=25.4% (n=107)1,4
- P<0.0001 for ORR1
mDOR at primary analysis (median follow-up time of 25.2 months)1,4
- Not yet reached (95% CI: 21.8–NE) for OPDIVO + YERVOY vs 18.2 months (95% CI: 14.8–NE) for sunitinib1,4
ORR†† at extended follow-up analysis (minimum follow-up time of 60 months)3
- OPDIVO + YERVOY: ORR: 42.1% (n=179/425 [95% CI: 37.4–47.0]; CR: 11.3% [n=48/425]; PR: 30.8% [n=131/425])3
- Sunitinib: ORR: 26.8% (n=113/422 [95% CI: 22.6–31.3]; CR: 2.1% [n=9/422]; PR: 24.6% [n=104/422]3
mDOR†† at extended follow-up analysis (minimum follow-up time of 60 months)3
- Not yet reached (95% CI: 50.9–NE) for OPDIVO + YERVOY vs 19.7 months (95% CI: 15.4–25.1) for sunitinib3
- HR=0.46 (95% CI: 0.31–0.66)3
In the 1L treatment of intermediate/poor risk aRCC
85.4% of complete responses to OPDIVO + YERVOY were ongoing at 5 years3
ORR†† at primary analysis (median follow-up time of 25.2 months)1,4
- OPDIVO + YERVOY: ORR: 41.6% (n=177/425 [95% CI: 36.9–46.5]; CR: 9.4% [n=40]; PR: 32.2% [n=137])1,4
- Sunitinib: ORR: 26.5% (n=112/422 (95% CI: 22.4–31.0); CR: 1.2% [n=5]; PR: 25.4% [n=107])1,4
- P<0.0001 for ORR1
ORR‡‡ at extended follow-up analysis (minimum follow-up time of 60 months)3
- OPDIVO + YERVOY: ORR: 42.1% (n=179/425) (95% CI: 37.4–47.0); CR: 11.3% [n=48/425]; PR: 30.8% [n=131/425]
- Sunitinib: ORR 26.8% (n=113/422 [95% CI: 22.6–31.3]; CR: 2.1% [n=9]; PR: 24.6% [n=104])
††At both the primary analysis and the extended follow-up analysis, ORR was assessed by an independent radiographic review committee per RECIST v1.1.1,3,4
Selected Safety Profile
The chance for long-term durability with a well-known safety profile1
Checkmate 214: fewer overall Grade 3-4 adverse reactions in
the OPDIVO + YERVOY arm vs sunitinib (65% vs 76%, respectively)1
OPDIVO + YERVOY (n=547) | Sunitinib (n=535) | |||
---|---|---|---|---|
Adverse reactions | Grades 1-4 | Grades 3-4 | Grades 1-4 | Grades 3-4 |
Adverse reactions, % All causes | 99 | 65 | 99 | 76 |
General disorders and Fatigue‡‡ | 58 25 16 | 8 0.7 0.5 | 69 17 17 | 13 0.6 0.6 |
Respiratory, thoracic, and mediastinal disorders, % Cough/productive cough Dyspnea/exertional dyspnea | 28 20 | 0.2 2.4 | 25 21 | 0.4 2.1 |
Gastrointestinal disorders, % Diarrhea | 38 30 20 19 17 | 4.6 2.0 0.9 1.6 0.4 | 58 43 28 24 18 | 6 1.5 2.1 1.9 0 |
Skin and subcutaneous Rash|||| | 39 33 | 3.7 0.5 | 25 11 | 1.1 0 |
Endocrine disorders, % Hypothyroidism | 18 | 0.4 | 27 | 0.2 |
Nervous system disorders, % Headache | 19 | 0.9 | 23 | 0.9 |
Metabolism and Decreased appetite | 21 | 1.8 | 29 | 0.9 |
Musculoskeletal and connective tissue disorder, % Musculoskeletal pain¶¶ Arthralgia | 37 23 | 4.0 1.3 | 40 16 | 2.6 0 |
OPDIVO + YERVOY (n=547) | Sunitinib (n=535) | |
---|---|---|
Adverse reactions | Grades 1-4 | Grades 1-4 |
Adverse All causes | 99 | 99 |
General Fatigue‡‡ | 58 25 16 | 69 17 17 |
Respiratory, thoracic, and mediastinal disorders, % Cough/ | 28 20 | 25 21 |
Gastrointestinal disorders, % Diarrhea | 38 30 20 19 17 | 58 43 28 24 18 |
Skin and subcutaneous tissue Rash|||| | 39 33 | 25 11 |
Endocrine disorders, % Hypothyroidism | 18 | 27 |
Nervous Headache | 19 | 23 |
Metabolism Decreased appetite | 21 | 29 |
Musculo- Musculo- | 37 23 | 40 16 |
OPDIVO + YERVOY (n=547) | Sunitinib (n=535) | |
---|---|---|
Adverse reactions | Grades 3-4 | Grades 3-4 |
Adverse All causes | 65 | 76 |
General Fatigue‡‡ | 8 0.7 0.5 | 13 0.6 0.6 |
Respiratory, thoracic, and mediastinal disorders, % Cough/ | 0.2 2.4 | 0.4 2.1 |
Gastrointestinal disorders, % Diarrhea | 4.6 2.0 0.9 1.6 0.4 | 6 1.5 2.1 1.9 0 |
Skin and subcutaneous tissue Rash|||| | 3.7 0.5 | 1.1 0 |
Endocrine disorders, % Hypothyroidism | 0.4 | 0.2 |
Nervous Headache | 0.9 | 0.9 |
Metabolism Decreased appetite | 1.8 | 0.9 |
Musculo- Musculo- | 4.0 1.3 | 2.6 0 |
- In the 60-month follow-up analysis, all-cause adverse events occurring in >15% of patients receiving OPDIVO + YERVOY and not previously included in the primary analysis include: upper respiratory tract infection (OPDIVO + YERVOY: 21.6% Grades 1-4; 0.4% Grades 3-4; sunitinib: 15.0% Grades 1-4)12
Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.1
‡‡Includes asthenia.1
§§Includes peripheral edema, peripheral swelling.1
||||Includes dermatitis described as acneiform, bullous, and exfoliative, drug eruption, rash described as exfoliative,
erythematous, follicular, generalized, macular, maculopapular, papular, pruritic, and pustular, fixed-drug eruption.1
¶¶Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity,
spinal pain.1
Checkmate 214: Grade 1-4 laboratory abnormalities that occurred
in >15% of patients on OPDIVO + YERVOY1
Percentage of patients with worsening laboratory test from baseline1##
OPDIVO + YERVOY (n=547) | Sunitinib (n=535) | |||
---|---|---|---|---|
Laboratory abnormalities | Grades 1-4 | Grades 3-4 | Grades 1-4 | Grades 3-4 |
Hematology Anemia | 43 36 | 3 5 | 64 63 | 9 14 |
Chemistry Increased lipase | 48 42 41 40 39 39 29 29 21 16 | 20 2.1 7 4.8 12 10 2 2.4 0.4 0.4 | 51 46 44 60 33 36 32 28 35 26 | 20 1.7 2.7 2.1 7 7 1 2.9 0.6 1.6 |
OPDIVO + YERVOY (n=547) | Sunitinib (n=535) | |
---|---|---|
Laboratory abnormalities | Grades 1-4 | Grades 1-4 |
Hematology Anemia | 43 36 | 64 63 |
Chemistry Increased lipase | 48 42 41 40 39 39 29 29 21 16 | 51 46 44 60 33 36 32 28 35 26 |
OPDIVO + YERVOY (n=547) | Sunitinib (n=535) | |
---|---|---|
Laboratory abnormalities | Grades 3-4 | Grades 3-4 |
Hematology Anemia | 3 5 | 9 14 |
Chemistry Increased lipase | 20 2.1 7 4.8 12 10 2 2.4 0.4 0.4 | 20 1.7 2.7 2.1 7 7 1 2.9 0.6 1.6 |
##Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory
measurement available: OPDIVO + YERVOY group (range: 490–538 patients) and sunitinib group (range: 485–523 patients).1
In addition, among patients with TSH less than or equal to the ULN at baseline, a lower proportion of patients experienced
a treatment-emergent elevation of TSH greater than the ULN in the OPDIVO + YERVOY group compared to the sunitinib
group (31% and 61%, respectively).1
- A lower incidence of overall Grade 3-4 adverse reactions occurred with OPDIVO + YERVOY vs
sunitinib (65% and 76%, respectively)1 - Treatment discontinuation rate due to adverse reactions was 31% with OPDIVO + YERVOY vs 21%
with sunitinib1,13 - Dose interruption due to adverse reactions occurred in 54% of patients receiving OPDIVO +
YERVOY and 43% receiving sunitinib1,14- In the sunitinib group, 53% of patients required a dose reduction; dose reductions were not
permitted in the OPDIVO + YERVOY treatment group15
- In the sunitinib group, 53% of patients required a dose reduction; dose reductions were not
- Serious adverse reactions occurred in 59% of patients receiving OPDIVO + YERVOY and in 43% of
patients receiving sunitinib1,16- The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO +
YERVOY were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury,
dyspnea, adrenal insufficiency, and colitis; for sunitinib, they were pneumonia, pleural effusion,
and dyspnea1
- The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO +
- The most common adverse reactions (reported in at least 20% of OPDIVO + YERVOY-treated
patients) were fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia,
arthralgia, decreased appetite, dyspnea, and vomiting1
IMAR Safety Management Resources
The OPDIVO Safety Tool is a quick reference to the immune-mediated adverse reactions (IMARs) associated with OPDIVO treatment. You may access this web app from your phone, tablet, or computer.
OPDIVO HCP RESOURCES
1L=first-line; ALT=alanine aminotransferase; aRCC=advanced renal cell carcinoma; AST=aspartate aminotransferase;
CI=confidence interval; CR=complete response; DOR=duration of response; HR=hazard ratio; IMDC=International Metastatic
Renal Cell Carcinoma Database Consortium; I-O=immuno-oncology; IV=intravenous; LLN=lower limit of normal;
mDOR=median duration of response; NE=not evaluable; No.=number; ORR=overall response rate; OS=overall survival;
PD-L1=programmed death-ligand 1; PFS=progression-free survival; PR=partial response; PS=performance score;
RCC=renal cell carcinoma; RECIST=Response Evaluation Criteria In Solid Tumors; TSH=thyroid-stimulating hormone; ULN=upper limit of normal.