KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma
Head to head, the PD-1 antibody pembrolizumab held melanoma back longer, prolonged life and caused fewer severe side effects than ipilimumab, the CTLA-4 antibody that had been the first immunotherapy to extend survival.
Overview
KEYNOTE-006 randomised 834 patients with advanced melanoma, most untreated with immunotherapy, to pembrolizumab every two weeks, pembrolizumab every three weeks, or ipilimumab. Both pembrolizumab schedules improved progression-free and overall survival and roughly tripled the response rate compared with ipilimumab, with fewer grade 3 to 5 treatment-related adverse events. The trial made PD-1 blockade the first-line immunotherapy standard in melanoma and showed the three-weekly schedule was as effective as the two-weekly one.
- 834 patients with advanced melanoma; pembrolizumab every 2 weeks, every 3 weeks, or ipilimumab.
- Six-month progression-free survival 47.3% and 46.4% vs 26.5%; hazard ratios 0.58.
- Twelve-month overall survival 74.1% and 68.4% vs 58.2%; hazard ratios 0.63 and 0.69.
- Response rates 33.7% and 32.9% vs 11.9%; grade 3 to 5 treatment-related adverse events 13.3% and 10.1% vs 19.9%.
This trial settled which checkpoint to block first in melanoma and set the pattern for PD-1 antibodies displacing ipilimumab across cancers. Long-term follow-up later showed that many responders remained free of progression years after stopping treatment.
- Open-label design.
- Ipilimumab was given at 3 mg/kg for four doses; the comparison does not cover combination therapy.
- Most patients had received no prior systemic therapy, so results apply mainly to first-line use.
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