Metastatic melanoma: How patients are gaining a decade with immunotherapy

In 2011, the median survival for patients with metastatic melanoma was just six-and-a-half months, but the results of a recent 10-year clinical trial in 21 countries could significantly improve this statistic.In this study, a total of 945 patients with advanced melanoma were assigned to one of three immune checkpoint inhibitors: a combination of nivolumab (anti-PD1) and ipilimumab (anti-CTLA-4), nivolumab monotherapy or ipilimumab monotherapy. The findings were published in the New England Journal of Medicine.The immunotherapy combination of nivolumab and ipilimumab achieved the best results in terms of patient survival. Median survival was 72 months, and 43% of patients were still alive at the 10-year followup. For patients treated with nivolumab alone, median survival was 36.9 months, with a third of patients surviving beyond 10 years. As for ipilimumab, median survival was just 20 months, with just 19% of patients surviving to the decade following treatment. In addition, additional systemic treatments were administered less frequently in the group receiving combined immunotherapy.Three-year markerPassing the three-year mark without progression of the disease appears to be a turning point in the long-term prognosis of patients. Such patients are more likely to survive for up to 10 years. In fact, of the patients who were still alive after three years' followup, 96% of those treated with nivolumab and ipilimumab, and 97% of those treated as monotherapy with nivolumab, still had no trace of melanoma a decade after treatment."Progression-free survival at three years appears to be a marker of long-term survival in patients with advanced melanoma treated with immune checkpoint inhibitors," the researchers noted. "These results may help determine the appropriate frequency of followup to detect further progression or new lesions in these patients." Despite these encouraging results, about 40% of patients respond poorly or not at all to the combination of checkpoint inhibitors. A phase 1/2 study is currently testing the efficacy of an immunotherapy involving three players. Therapy combining nivolumab, relatimab and ipilimumab showed a 69% survival rate at 48-month followup, suggesting that some patients who do not respond to current treatments could benefit from this triple therapy.Although no new signs of toxicity emerged during this phase of the study, ipilimumab administered alone or in combination with nivolumab is known to frequently cause adverse events, including skin problems and disorders of the gastrointestinal system. Nivolumab combined with relatimab would offer similar results to the nivolumab/ipilimumab combination in terms of survival, but with far fewer adverse events associated with stage 3 or 4 treatment.

Metastatic melanoma: How patients are gaining a decade with immunotherapy

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