Do Long-Term Outcomes Support Combination Immunotherapy for Advanced Melanoma?

In a 10-year follow-up of a clinical trial, researchers observed sustained survival benefits for patients with advanced melanoma treated with nivolumab plus ipilimumab or nivolumab monotherapy compared with ipilimumab alone. The combination therapy offered the greatest improvement, with median overall survival extending to nearly 6 years.

Advancements in immunotherapy have transformed the prognosis for patients with advanced melanoma, leading to longer survival times. However, with more patients living beyond 7.5 years, updated long-term data are needed for addressing new clinical questions about treatment durability and survival outcomes.

This trial randomized patients with previously untreated advanced melanoma in a 1:1:1 ratio to receive one of three regimens: nivolumab plus ipilimumab, nivolumab monotherapy, or ipilimumab monotherapy. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification factors included BRAF mutation status, metastasis stage, and programmed death ligand 1 expression.

After a minimum of 10 years of follow-up, the combination of nivolumab plus ipilimumab achieved a median overall survival of 71.9 months, compared with 36.9 months for nivolumab monotherapy and 19.9 months for ipilimumab monotherapy. The hazard ratio for death was 0.53 (95% CI, 0.44–0.65) for nivolumab plus ipilimumab versus ipilimumab alone, and 0.63 (95% CI, 0.52–0.76) for nivolumab versus ipilimumab. Median melanoma-specific survival exceeded 120 months with nivolumab plus ipilimumab, 49.4 months with nivolumab, and 21.9 months with ipilimumab. For patients who had been alive and progression-free at 3 years, researchers observed 10-year melanoma-specific survival rates of 96% for nivolumab plus ipilimumab, 97% for nivolumab monotherapy, and 88% for ipilimumab.

“The final trial results showed a continued, ongoing survival benefit with nivolumab plus ipilimumab and with nivolumab monotherapy, as compared with ipilimumab monotherapy, in patients with advanced melanoma,” the study authors concluded.

Reference

Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. Published online September 15, 2024. doi:10.1056/NEJMoa2407417