| BASELINE CHARACTERISTICS | OPDIVO (n=526) | PLACEBO (n=264) |
|---|---|---|
| Median age, years (range) | 62 (21-87) | 61 (19-92) |
| Male, n (%) | 322 (61%) | 161 (61%) |
| ECOG PS 0, n (%) | 495 (94%) | 245 (93%) |
Stage, n (%) IIB |
316 (60%) |
163 (62%) |
T category, n (%) T3b |
204 (39%) |
104 (39%) |
Melanoma subtype, n (%) Nodular |
266 (51%) |
133 (50%) |
Region, n (%) Western Europe |
303 (58%) |
160 (61%) |
Adjuvant Treatment of Melanoma
Approved in Stage IIB/C, III, IV
Bring the benefit of OPDIVO® to more patients1
INDICATION OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
Nivolumab (OPDIVO) is a NCCN Category 1 recommended adjuvant treatment option for completely resected pathological stage IIB/C cutaneous melanoma in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)2
NCCN=National Comprehensive Cancer Network® (NCCN®).
CHECKMATE 76K: IN ADULT AND PEDIATRIC PATIENTS 12 YEARS AND OLDER WITH COMPLETELY RESECTED STAGE IIB/C MELANOMA
Checkmate 76K evaluated RFS with OPDIVO q4w as adjuvant treatment for eligible patients with completely resected stage IIB/C melanoma1,3
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL1,3
*See Full Prescribing Information for recommended dosing information.
DMFS=distant metastasis-free survival; ECOG PS=Eastern Cooperative Oncology Group Performance Score; IV=intravenous; OS=overall survival; PFS2=progression-free survival through next-line therapy; q4w=every 4 weeks; R=randomization; RFS=recurrence-free survival.
Patient baseline characteristics3
*Categorized as desmoplastic melanoma (n=21 [4%]), lentigo maligna (n=13 [2%]), “other” (n=44 [8%]), and not reported (n=3 [1%]).
†Categorized as desmoplastic melanoma (n=8 [3%]), lentigo maligna (n=3 [1%]), “other” (n=22 [8%]), and not reported (n=1 [<1%]).
Select Important Safety Information
Serious Adverse Reactions
In Checkmate 76K, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=524). Adverse reactions which resulted in permanent discontinuation of OPDIVO in >1% of patients included arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%). A fatal adverse reaction occurred in 1 (0.2%) patient (heart failure and acute kidney injury). The most frequent Grade 3-4 lab abnormalities reported in ≥1% of OPDIVO-treated patients were increased lipase (2.9%), increased AST (2.2%), increased ALT (2.1%), lymphopenia (1.1%), and decreased potassium (1.0%).
Please see additional Important Safety Information below.
At the primary analysis, OPDIVO reduced the risk of recurrence* or death by 58% compared to placebo1,3
AT THE ~34-MONTH MEDIAN FOLLOW-UP, THE RFS HR WAS 0.62 FOR OPDIVO VS PLACEBO4†
RECURRENCE-FREE SURVIVAL RESULTS AT ~34-MONTH MEDIAN FOLLOW-UP ANALYSIS1,3,4†‡
*Recurrence includes new primary melanoma.1
†Median follow-up was 34.2 months for the OPDIVO group and 33.9 months for the placebo group.4
‡The follow-up analysis is not powered to assess statistical significance.
RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis), new primary melanoma, or death, from any cause, whichever occurred first and as assessed by the investigator.1
CI=confidence interval; HR=hazard ratio; NR=not reached.
At ~34-month median follow-up, an HR of 0.72 was observed for DMFS for OPDIVO vs placebo4*
SECONDARY ENDPOINT: DMFS RESULTS AT ~34-MONTH MEDIAN FOLLOW-UP ANALYSIS4*
- HR vs placebo (95% CI): 0.72 (0.52–1.00)4
- Median DMFS, mos (95% CI): NR with OPDIVO (n=526) and NR with placebo (n=264)4
- DMFS was not assessed for statistical significance4
DMFS is defined as the time between the date of randomization and the date of first distant metastasis or date of death (whichever the cause), whichever occurred first.5
*Median follow-up was 34.2 months for the OPDIVO group and 33.9 months for the placebo group.4
NA=not available.
Select Important Safety Information
Common Adverse Reactions
In Checkmate 76K, the most common adverse reactions (≥20%) reported with OPDIVO (n=524) were fatigue (36%), musculoskeletal pain (30%), rash (28%), diarrhea (23%) and pruritis (20%).
Please see additional Important Safety Information below.
Higher RFS rates observed regardless of disease stage or T category with OPDIVO4*†
RFS DATA BY SUBGROUP WITH UNSTRATIFIED HR AT ~34-MONTH MEDIAN FOLLOW-UP ANALYSIS4†
These analyses were exploratory and not powered.
*vs placebo.
†Median follow-up was 34.2 months for the OPDIVO group and 33.9 months for the placebo group.4
N=number.
OPDIVO dosing options1*
- OPDIVO is administered over 30 minutes as an intravenous infusion1
- Based on exploratory dose exposure-response relationships for efficacy and safety, OPDIVO 240 mg q2w and 480 mg q4w are predicted to be similar6
- Review the U.S. Full Prescribing Information for recommended dosage information for OPDIVO
- No premedication required1
*For pediatric patients age 12 years and older and weighing less than 40 kg, OPDIVO dosing is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks (30-minute IV infusion) until disease recurrence or unacceptable toxicity for up to 1 year.1
†For adult and pediatric patients 12 years and older who weigh 40 kg or more.1
CHECKMATE 238: ADJUVANT TREATMENT OF MELANOMA
The only head-to-head clinical trial to evaluate a current standard of care* vs an active comparator with proven OS benefit1,2,7-9
Similar to the real-world population, Checkmate 238 included 42% BRAF mutant patients1,10
*Based on the primary analysis for Study CA 184-029, the OS HR of YERVOY® (ipilimumab) vs placebo was 0.72 (95% CI, 0.58 to 0.88); P<0.002. At median follow-up of 5.3 years, the OS was 65.4% (95% CI, 60.8 to 69.6) in the ipilimumab group, as compared with 54.4% (95% CI, 49.7 to 58.9) in the placebo group at 5 years.8,11
†OS in Checkmate 238 did not meet statistical significance.1
AJCC=American Joint Committee on Cancer; BRAF=B-Raf proto-oncogene; CI=confidence interval; HR=hazard ratio; IV=intravenous; NED=no evidence of disease; OS=overall survival; PD-L1=programmed death-ligand 1; q2w=every 2 weeks; q3w=every 3 weeks; q12w=every 12 weeks; RFS=recurrence-free survival.
Select Important Safety Information
Serious Adverse Reactions
In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO® (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase.
Please see additional Important Safety Information below.
Durable RFS benefit and the longest follow-up for any PD-1 agent in the adjuvant setting for melanoma1,7,9,12-14
RECURRENCE-FREE SURVIVAL RESULTS THROUGH 7 YEARS
Median RFS, mos (95% CI):
- 18 months (ITT): OPDIVO 3 mg/kg: NR (NR–NR); YERVOY 10 mg/kg: NR (16.6–NR)1,9
- 7 years (ITT): OPDIVO 3 mg/kg: 61.1 (42.9–NR); YERVOY 10 mg/kg: 24.2 (16.6–35.1)7
- RFS by BRAF status was an exploratory pre-specified subgroup analysis at 18 months and at 7 years1,7,9
- 7-year RFS rate in patients receiving YERVOY was 39%* for BRAF MT and 35%* for BRAF WT7
- 7-year RFS in BRAF MT: 68.6 for OPDIVO (35.0–NR), 25.5 for YERVOY (15.9–55.1)7
- 7-year RFS in BRAF WT: 50.2 for OPDIVO (36.3–NR), 16.6 for YERVOY (11.6–35.1)7
*These data are based on RFS Kaplan-Meier estimates.7
†Unstratified hazard ratio.7
ITT=intent to treat; MT=mutant; NR=not reached; PD-1=programmed cell death protein-1; WT=wild-type.
Select Important Safety Information
Common Adverse Reactions
In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%).
Please see additional Important Safety Information below.
RFS rates were numerically similar across BRAF status through 7 years7
RFS IN BRAF MUTANT
RFS IN BRAF WILD-TYPE
RFS by BRAF status was an exploratory pre-specified analysis at 18 months and 7 years.7,9
*Unstratified hazard ratio.7
N=number.
Recurrence-free survival in patients with stages III and IV (NED) through 7 years15
Stage IIIB/C RFS
Stage IV (NED) RFS
STAGE IIIB/C RFS AT 7-YEAR FOLLOW-UP ANALYSIS
- Stage IIIB: 53%† for OPDIVO vs 46%† for YERVOY; HR=0.73 (95% CI: 0.53–1.01)7
- Stage IIIC: 39%† for OPDIVO vs 34%† for YERVOY; HR=0.78 (95% CI: 0.60–1.00)7
- Not reported: 1 of 1 for OPDIVO and 0 of 0 for YERVOY7
- RFS by stages IIIB/C and IV (NED) was a post hoc analysis at 7 years. Melanoma stages IIIB, IIIC, and IV (NED) were assessed per AJCC 7th edition1,7
*Unstratified HR.15
†These data are based on RFS Kaplan-Meier estimates.15
NA=not available.
OPDIVO dosing options1*
- OPDIVO is administered over 30 minutes as an intravenous infusion1
- Based on exploratory dose exposure-response relationships for efficacy and safety, OPDIVO 240 mg q2w and 480 mg q4w are predicted to be similar6
- Review the U.S. Full Prescribing Information for recommended dosage information for OPDIVO
- No premedication required1
*For pediatric patients age 12 years and older and weighing less than 40 kg, OPDIVO dosing is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks (30-minute IV infusion) until disease recurrence or unacceptable toxicity for up to 1 year.1
†For adult and pediatric patients 12 years and older who weigh 40 kg or more.1
q4w dosing offers a balance for both patient and provider needs1,16
Balance extended time between infusions with the confidence of regular monitoring
Help control patient adherence concerns with IV administration regardless of BRAF mutation status1
- Infusions may reduce adherence concerns and can be coordinated with patients’ monthly follow-up visits16
- No in-home refrigeration, meal restrictions, and/or treatment pill burden for patients1*‡
*This content is not intended to imply comparative efficacy between OPDIVO dosing schedules. Selection of approved dosing frequency should be based on independent clinical judgment.
†For pediatric patients age 12 years and older and weighing less than 40 kg, OPDIVO dosing is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks (30-minute IV infusion) until disease recurrence or unacceptable toxicity for up to 1 year.1
‡Please see the OPDIVO Full Prescribing Information for guidance on storage and refrigeration.
Safety Data
View a selected safety profile of adverse reactions seen in clinical trials.
Dosing Schedules
Find dosing information to get patients started on therapy.
More Melanoma Options
Learn more about all melanoma indications.
Learn more about how OPDIVO is approved for use in earlier stages of cancer
References:
- OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma: Cutaneous V.3.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 24, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
- Kirkwood JM, Del Vecchio M, Weber J, et al. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med. 2023;29(11):2835-2843.
- Long GV, Del Vecchio M, Hoeller C, et al. Adjuvant nivolumab versus placebo in stage IIB/C melanoma: 3-year results from CheckMate 76K. Presented at ESMO 2024. Presentation number 1077MO.
- Effectiveness study of nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/C melanoma (CheckMate76K). ClinicalTrials.gov identifier: NCT04099251. https://classic.clinicaltrials.gov/ct2/show/NCT04099251. Updated July 27, 2023. Accessed August 10, 2023.
- Long GV, Tykodi SS, Schneider JG, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018;29(11):2208-2213.
- Ascierto PA, Del Vecchio M, Merelli B, et al. Adjuvant nivolumab versus ipilimumab in resected stage III/IV melanoma: 7-year results from CheckMate 238. Presented at ESMO 2023. Abstract 1089P.
- Eggermont AMM, Chiarion-Sileni V, Grob J-J, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845-1855.
- Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824-1835.
- Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol. 2018;31(1):24-38.
- YERVOY [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
- Ascierto PA, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2020;21(11):1465-1477.
- Weber J, Del Vecchio M, Mandala M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III/IV melanoma: 3-year efficacy and biomarker results from the phase 3 CheckMate 238 trial. Presented at ESMO 2019. Abstract 2801.
- Weber J, Larkin J, Mandalá M, et al. Five-year outcomes with adjuvant nivolumab versus ipilimumab in resected stage IIIB-C or IV melanoma (CheckMate 238). Oral presentation at SMR 2021.
- Data on file. BMS-REF-NIVO-0253. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
- Seal BS, Anderson S, Shermock KM. Factors associated with adherence rates for oral and intravenous anticancer therapy in commercially insured patients with metastatic colon cancer. J Manag Care Spec Pharm. 2016;22(3):227-235.