Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE 006: A randomised clinical trial.
BACKGROUND Predictive biomarkers of patients likely to benefit from anti programmed death 1 inhibitor therapy have clinical relevance. We examined whether line of therapy or tumour programmed death ligand 1 (PD L1) expression affects the efficacy and safety of pembrolizumab, compared with ipilimumab, in advanced melanoma. METHODS Of 834 patients enrolled in the randomised, open label phase III KEYNOTE 006 study, 833 were included in this analysis. Patients were randomly assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 or 3 weeks (for 24 months) or ipilimumab 3 mg/kg every 3 weeks (for four doses) until disease progression/intolerable toxicity. This analysis evaluated progression free survival (PFS) overall survival (OS) and objective response rate (ORR) Data cut off: 03 November 2016. RESULTS Of the patients, 60.3% were male, 65.9% were treatment naive and 80.6% had PD L1 positive tumours (median follow up was 33.9 months) Twenty four month survival rates were higher with pembrolizumab than with ipilimumab in treatment naive (PFS 31.0% versus 14.6% OS 58.0% versus 44.7% and previously treated patients (PFS 25.7% versus 11.3% OS 49.2% versus 37.9% Twenty four month survival rates were higher with pembrolizumab than with ipilimumab in patients with PD L1 positive tumours (PFS 33.2% versus 13.1% OS 58.4% versus 45.0% and similar in PD L1 negative tumours (PFS 14.9% versus NR [no data at 24 months for a PFS estimate] OS 43.6% versus 31.8% Safety of pembrolizumab by subgroup was consistent with previous reports. CONCLUSIONS Findings support pembrolizumab monotherapy as standard of care in patients with advanced melanoma, regardless of first or second line therapy or PD L1 status. CLINICALTRIALS. GOV IDENTIFIER NCT01866319.
European journal of cancer