10-year follow-up data from the Phase 3 CheckMate-067 clinical trial (NCT01844505) demonstrated continued durable improvements in survival with nivolumab (Opdivo; Bristol Myers Squibb) and ipilimumab (Yervoy; Bristol Myers Squibb) in first-line treatment for patients with previously untreated advanced or metastatic melanoma. The results, presented at the European Society for Medical Oncology Congress 2024, represent significant progress in the treatment of advanced melanoma, a diagnosis that has historically had a poor prognosis.1
At 10 years of follow-up, median OS for participants treated with nivolumab and ipilimumab was 71.9 months. Image credit: © Shutter2U – stock.adobe.com
According to the World Health Organization, approximately 424,000 individuals will be diagnosed with melanoma by 2025, emphasizing the critical need for improved medical interventions. It is a skin cancer characterized by the uncontrolled growth of melanocytes on the skin. The mechanism behind melanoma is unclear; however, researchers speculate that prolonged exposure to ultraviolet light may be a risk factor. Metastatic melanoma occurs when cancer spreads from the skin to other organs and is the most deadly form of the disease.2,3
Treatment interventions may vary between patients, but generally include surgery, radiation therapy and chemotherapy, as well as novel immunotherapy. The advent of immunotherapy treatments has improved health outcomes for patients with advanced or metastatic melanoma. In the randomized, double-blind, Phase 3 CheckMate-067 trial, researchers evaluated the efficacy of nivolumab in combination with ipilimumab compared to ipilimumab as monotherapy. According to their findings, the combination treatment delivered a sustained durable improvement in survival, offering hope for patients suffering from aggressive disease and poor prognosis.2,3
“More than a decade ago, an advanced diagnosis of melanoma meant you had only a few months to live,” Dana Walker, MD, MSCE, vice president and global program leader for melanoma and gastrointestinal and genitourinary cancers at Bristol Myers Squibb, said in a news release. “Combining dual immunotherapy [nivolumab] Plus [ipilimumab] This has fundamentally changed the outlook for many of these patients.”2
Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to use the body's own immune system to restore anti-tumor immune responses. As of 2024, it has been approved in more than 65 countries, including the US, Europe, Japan, and China. It is also approved as a combination treatment with ipilimumab, a recombinant, human monoclonal antibody. Ipilimumab works by binding to cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), a negative regulator of T-cell activity. Blocking CTLA-4 has been shown to increase T-cell activation and proliferation, thereby inhibiting CTLA-4 signaling.2
In the study, researchers randomly assigned 945 patients in a 1:1:1 ratio to receive 1 of the following regimens: nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for 4 doses, followed by nivolumab (3 mg per kilogram) every 2 weeks (n=314); nivolumab (3 mg per kilogram) every 2 weeks plus placebo (n=316); or ipilimumab (3 mg per kilogram) every 3 weeks for 4 doses plus placebo (n=315). The primary endpoints of the trial were overall survival (OS) and progression-free survival, while secondary endpoints were objective response rate, efficacy, and safety.2,4
At 10 years of follow-up, median OS for participants treated with nivolumab and ipilimumab was 71.9 months (95% CI: 38.2-114.4), compared with 36.9 months with nivolumab monotherapy (95% CI: 28.2-58.7) and 19.9 months with ipilimumab monotherapy (95% CI: 16.8-24.6). Data demonstrated a median melanoma-specific survival rate of over 120 months with the combination treatment compared with nivolumab (49.4 months) or ipilimumab (21.9 months).2,4
The safety of nivolumab and ipilimumab was consistent with previous findings, with no new concerns and no treatment-related deaths. Of the participants, 62.6% of patients in the combination group, 24.6% of patients in the nivolumab group, and 29.6% of patients in the ipilimumab group experienced grade 3 or 4 treatment-related adverse events.2,4
“These data continue to demonstrate the impressive and durable clinical benefit of combining ipilimumab with nivolumab, with survival rates remaining stable over the last few years,” James Larkin, PhD, FRCP, consultant medical oncologist in the department of medical oncology at The Royal Marsden, said in a news release. “Remarkably, 43% of patients treated with nivolumab and ipilimumab are alive after 10 years and many did not require subsequent treatment.”2
The results of the clinical trial have important implications for the evolving treatment landscape for skin cancer, bringing new hope to patients. Continued innovations in treatments for this disease are critical to effectively address aggressive disease in patients with advanced or metastatic melanoma.