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

• Published in: European journal of cancer (1990) 2018-09, Vol.101, p.236-243
• Main Authors: Carlino, Matteo S., Long, Georgina V., Schadendorf, Dirk, Robert, Caroline, Ribas, Antoni, Richtig, Erika, Nyakas, Marta, Caglevic, Christian, Tarhini, Ahmed, Blank, Christian, Hoeller, Christoph, Bar-Sela, Gil, Barrow, Catherine, Wolter, Pascal, Zhou, Honghong, Emancipator, Kenneth, Jensen, Erin H., Ebbinghaus, Scot, Ibrahim, Nageatte, Daud, Adil
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - metabolism; Biomarkers; Cancer therapies; Clinical trials; Death; Drug Administration Schedule; Female; Humans; Immunotherapy; Ipilimumab - adverse effects; Ipilimumab - therapeutic use; Kaplan-Meier Estimate; Ligands; Male; Melanoma; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - pathology; Middle Aged; Monoclonal antibodies; Mortality; Patients; PD-1; PD-1 protein; PD-L1; PD-L1 protein; Pembrolizumab; Randomization; Safety; Subgroups; Survival; Targeted cancer therapy; Therapy; Toxic diseases; Toxicity; Treatment Outcome; Tumors; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2018.06.034

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. 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. 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. Findings support pembrolizumab monotherapy as standard of care in patients with advanced melanoma, regardless of first- or second-line therapy or PD-L1 status. NCT01866319. •Response rates were higher with pembrolizumab than with ipilimumab, regardless of line of therapy.•Response rates were higher with pembrolizumab irrespective of tumour programmed death ligand 1 (PD-L1) expression.•Survival was superior with pembrolizumab in PD-L1–positive tumours and comparable to ipilimumab in PD-L1–negative tumours.•Findings support pembrolizumab use with advanced melanoma, regardless of line of prior therapy or PD-L1 status.