Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma

Eur J Cancer. 2016 Nov;67:46-54. doi: 10.1016/j.ejca.2016.07.018. Epub 2016 Sep 2.


Background: In KEYNOTE-002, pembrolizumab significantly prolonged progression-free survival and was associated with a better safety profile compared with chemotherapy in patients with advanced melanoma that progressed after ipilimumab. We present health-related quality of life (HRQoL) outcomes from KEYNOTE-002.

Methods: Patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or investigator-choice chemotherapy. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 instrument. A constrained longitudinal data analysis model was implemented to assess between-arm differences in HRQoL scores. The study is registered with, number NCT01704287.

Results: Of the 540 patients enrolled, 520 were included in the HRQoL analysis. Baseline global health status (GHS) was similar across treatment arms. Compliance rates at week 12 were 76.6% (n = 108), 82.3% (n = 121), and 86.4% (n = 133) for the control, pembrolizumab 2 mg/kg Q3W, and pembrolizumab 10 mg/kg Q3W arms, respectively. From baseline to week 12, GHS/HRQoL scores were maintained to a higher degree in the pembrolizumab arms compared with the chemotherapy arm (decrease of -2.6 for each pembrolizumab arm versus -9.1 for chemotherapy; P = 0.01 for each pembrolizumab arm versus chemotherapy). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31.8% for pembrolizumab 2 mg/kg, 26.6% for 10 mg/kg, and 38.3% for chemotherapy), with similar trends observed for the individual functioning and symptoms scales.

Conclusions: HRQoL was better maintained with pembrolizumab than with chemotherapy in KEYNOTE-002, supporting the use of pembrolizumab in patients with ipilimumab-refractory melanoma.

Keywords: Advanced melanoma; Chemotherapy; EORTC QLQ-C30; Health-related quality of life; Ipilimumab-refractory melanoma; KEYNOTE-002; Patient-reported outcomes; Pembrolizumab.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Health Status*
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Patient Reported Outcome Measures
  • Quality of Life*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Temozolomide
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Dacarbazine
  • Carboplatin
  • pembrolizumab
  • Paclitaxel
  • Temozolomide

Associated data