CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma
Ten years after starting treatment, about half of patients with advanced melanoma treated with nivolumab plus ipilimumab were still alive, most without any further treatment, showing that immunotherapy can cure a disease that once killed most patients within a year.
Final ten-year analysis of the double-blind phase 3 trial of 945 patients with untreated advanced melanoma randomised to nivolumab plus ipilimumab, nivolumab alone, or ipilimumab alone.
Median overall survival was 71.9 months with the combination, 36.9 months with nivolumab and 19.9 months with ipilimumab; 10-year OS was 43%, 37% and 19%. Median melanoma-specific survival was not reached for the combination, with 10-year melanoma-specific survival of 52%. The survival curves plateaued after about three years, and most surviving patients had been off treatment for years. It is the longest follow-up of any checkpoint inhibitor trial and the definitive evidence that immunotherapy can be curative.
- Median overall survival 71.9 months (nivolumab plus ipilimumab) vs 36.9 months (nivolumab) vs 19.9 months (ipilimumab).
- 10-year overall survival 43% vs 37% vs 19%; 10-year melanoma-specific survival 52% vs 44% vs 23%.
- Median melanoma-specific survival not reached for the combination (over 120 months) vs 49.4 months for nivolumab.
- Among patients alive at three years, subsequent melanoma deaths were rare, and most survivors had received no further systemic therapy.
- The combination versus nivolumab alone was not formally powered for comparison; grade 3-4 treatment-related adverse events were 59% vs 24% vs 28% in the original report.
For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.
- The trial was not designed to compare the combination with nivolumab alone, and that difference is not statistically established.
- Toxicity of the combination is substantial, with roughly one in three patients stopping for adverse events.
- Patients were treated before BRAF/MEK inhibitors and relatlimab were standard, so sequencing questions are not answered.
- Predicting who is cured versus who relapses late is still not possible from baseline biomarkers.
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