• Matteo S Carlino, Georgina V Long, Dirk Schadendorf, Caroline Robert, Antoni Ribas, Erika Richtig, Marta Nyakas, Christian Caglevic, Ahmed Tarhini, Christian Blank, Christoph Hoeller, Gil Bar-Sela, Catherine Barrow, Pascal Wolter, Honghong Zhou, Kenneth Emancipator, Erin H Jensen, Scot Ebbinghaus, Nageatte Ibrahim, and Adil Daud.
• Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia; School of Medicine, University of Sydney, Sydney, NSW, Australia. Electronic address: Matteo.carlino@sydney.edu.au.
• Eur. J. Cancer. 2018 Sep 1; 101: 236-243.

BackgroundPredictive 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.MethodsOf 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.ResultsOf 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.ConclusionsFindings 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 IdentifierNCT01866319.Copyright © 2018 Elsevier Ltd. All rights reserved.

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