Long-Term Survival Rates Improve with Dual Immunotherapy in Metastatic Melanoma
Ten-year follow up data showed a sustained survival benefit with nivolumab-ipilimumab in advanced melanoma.
Data from the 10-year follow up of 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 the first line for patients with previously untreated advanced or metastatic melanoma. The results, presented at the European Society for Medical oncology Congress 2024, mark significant advancements in treatment for advanced melanoma, a diagnosis that has historically had poorer prognoses.1
At the 10-year follow up, participants receiving treatment with nivolumab and ipilimumab had a median OS of 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 crucial need for improved medical interventions. It is a skin cancer characterized by the uncontrolled growth of melanocytes on the skin. The mechanism underlying melanoma is unclear; however, researchers hypothesize that prolonged exposure to ultraviolet light may be a risk factor. Metastatic melanoma occurs when the cancer spreads from the skin to other organs and is the most fatal form of the disease.2,3
Treatment interventions can vary across patients, but typically involves surgery, radiation therapy, and chemotherapy, as well as novel immunotherapies. The advent of immunotherapy treatments 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 with ipilimumab as a monotherapy. According to their findings, the combination treatment yielded continued durable improvement in survival, offering hope for patients burdened by aggressive disease and poor prognosis.2,3
“Just over a decade ago, an advanced melanoma diagnosis meant that you likely only had months to live,” Dana Walker, MD, MSCE, vice president and global program lead of melanoma and gastrointestinal and genitourinary cancers at Bristol Myers Squibb, said in a news release. “The dual immunotherapy combination of [nivolumab] plus [ipilimumab] has radically changed this outlook for many of these patients.”2
Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to harness the body’s own immune system to restore the anti-tumor immune response. As of 2024, it is approved in over 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 functions by binding to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), a negative regulator of T-cell activity. Blocking CTLA-4 has shown to increase T-cell activation and proliferation, thereby inhibiting CTLA-4 signaling.2
In the study, the 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 end points of the trial were overall survival (OS) and progression-free survival with secondary end points of objective response rates, efficacy, and safety.2,4
At the 10-year follow up, participants receiving treatment with nivolumab and ipilimumab had a median OS of 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). The 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 prior findings with no new concerns and there were 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 experience grade 3 or 4 treatment-related adverse events.2,4
“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,” James Larkin, PhD, FRCP, consultant medical oncologist with 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 10 years later and many did not need subsequent therapy.”2
The clinical trial results have crucial implications for the evolving treatment landscape for skin cancer, offering renewed hope for patients. Continued innovations in the treatment of this disease are crucial to effectively address aggressive disease in patients with advanced or metastatic melanoma.
