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

Eur J Cancer. 2018 Sep;101:236-243. doi: 10.1016/j.ejca.2018.06.034. Epub 2018 Aug 7.


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.

Keywords: Melanoma; PD-1; PD-L1; Pembrolizumab.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Drug Administration Schedule
  • Female
  • Humans
  • Ipilimumab / adverse effects
  • Ipilimumab / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Middle Aged
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • Ipilimumab
  • pembrolizumab

Associated data

  • ClinicalTrials.gov/NCT01866319