Bristol Myers Squibb (BMS) announced landmark 10-year follow-up data from the CheckMate-067 trial, revealing a 43% survival rate among patients with advanced melanoma treated with the combination of Opdivo (nivolumab) and Yervoy (ipilimumab). These findings, presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona and published in The New England Journal of Medicine, represent a significant advancement in the treatment of this aggressive skin cancer.
The study's results indicate a median overall survival (OS) of 71.9 months (95% CI: 38.2-114.4) for the combination therapy, the longest reported median OS in a Phase 3 trial for advanced melanoma. In comparison, patients treated with Opdivo alone had a median OS of 36.9 months (95% CI: 28.2-58.7), while those treated with Yervoy alone had a median OS of 19.9 months (95% CI: 16.8-24.6).
Durable Clinical Benefit
An impressive 64% of patients who received the Opdivo and Yervoy combination did not require any subsequent systemic therapy at the 10-year follow-up. This suggests a durable and sustained clinical benefit from the initial treatment regimen. In comparison, 50% of patients treated with Opdivo alone and 33% of those treated with Yervoy alone did not require subsequent therapy.
James Larkin, Ph.D., FRCP, Consultant Medical Oncologist at The Royal Marsden, noted, "These data continue to demonstrate the impressive and durable clinical benefit of nivolumab in combination with ipilimumab with survival curves remaining stable for some years now. Remarkably, 43% of patients treated with nivolumab and ipilimumab are alive ten years later and many did not need subsequent therapy."
Melanoma-Specific Survival
The study also reported melanoma-specific survival (MSS) rates at 10 years. The Opdivo plus Yervoy combination showed an MSS rate of 52% (median not reached), compared to 44% (median of 49.4 months) for Opdivo alone and 23% (median of 21.9 months) for Yervoy alone.
Impact on BRAF Mutation Subgroups
Durable benefits were observed across relevant subgroups, including patients with BRAF-mutant and BRAF wild-type tumors. Among patients with BRAF-mutant tumors, the OS rate at 10 years was 52% (95% CI: 42-62) for those receiving Opdivo plus Yervoy, 37% (95% CI: 27-46) for Opdivo alone, and 25% (95% CI: 17-34) for Yervoy alone. In patients with BRAF wild-type tumors, the OS rate at 10 years was 39% (95% CI: 32-46) for Opdivo plus Yervoy, 37% (95% CI: 31-44) for Opdivo alone, and 17% (95% CI: 12-23) for Yervoy alone.
Objective Response Rate and Safety
At 10 years, the objective response rate (ORR) was higher for the Opdivo groups, both in combination with Yervoy (58.3%) and as monotherapy (44.9%), compared to the Yervoy group (19.0%). The median duration of response (DoR) was not reached for the Opdivo plus Yervoy group, while it was 103.2 months for Opdivo-treated patients and 19.2 months for Yervoy-treated patients.
The safety profile of Opdivo plus Yervoy remained consistent with previous findings, with no new safety signals identified and no additional treatment-related deaths reported since prior analyses. Grade 3/4 treatment-related adverse events were reported in 62.6% of patients in the combination group, 24.6% in the Opdivo group, and 29.6% in the Yervoy group.
A Paradigm Shift in Melanoma Treatment
Dana Walker, M.D., M.S.C.E., vice president, global program lead, melanoma and gastrointestinal and genitourinary cancers, Bristol Myers Squibb, emphasized the transformative impact of the combination therapy: "Just over a decade ago, an advanced melanoma diagnosis meant that you likely only had months to live. The dual immunotherapy combination of Opdivo plus Yervoy has radically changed this outlook for many of these patients."
