Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study

G. V. Long*, M. S. Carlino, C. McNeil, A. Ribas, C. Gaudy-Marqueste, J. Schachter, M. Nyakas, D. Kee, T. M. Petrella, A. Blaustein, M. Lotem, A. M. Arance, A. I. Daud, O. Hamid, J. Larkin, L. Yao, R. Singh, R. Lal, C. Robert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Pembrolizumab significantly improved overall survival (OS) versus ipilimumab for unresectable advanced melanoma in KEYNOTE-006 (NCT01866319); 10-year follow-up data are presented. Patients and methods: Patients with unresectable stage III or IV melanoma were randomly assigned (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 weeks or every 3 weeks for ≤2 years (pooled), or ipilimumab 3 mg/kg i.v. every 3 weeks for four cycles. After KEYNOTE-006, patients could transition to KEYNOTE-587 (NCT03486873) for long-term follow-up. Eligible patients could receive second-course pembrolizumab. The primary endpoint was OS; modified progression-free survival (PFS; censored at date last known alive), modified PFS on second-course pembrolizumab, and melanoma-specific survival were exploratory. Results: Of 834 patients randomly assigned in KEYNOTE-006 (pembrolizumab, n = 556; ipilimumab, n = 278), 333 (39.9%) were eligible for KEYNOTE-587; 211/333 patients (25.3%) transitioned to KEYNOTE-587 (pembrolizumab, n = 159; ipilimumab, n = 52) and 122 (14.6%) did not. For patients who transitioned to KEYNOTE-587 (n = 211), median time from randomization in KEYNOTE-006 to data cut-off for KEYNOTE-587 (1 May 2024) was 123.7 months (range, 122.0-127.3 months). Median OS was 32.7 months [95% confidence interval (CI) 24.5-41.6 months] for pembrolizumab and 15.9 months (95% CI 13.3-22.0 months) for ipilimumab [hazard ratio (HR), 0.71 (95% CI 0.60-0.85)]; 10-year OS was 34.0% and 23.6%, respectively. Among patients who completed ≥94 weeks of pembrolizumab, median OS from week 94 was not reached (NR; 95% CI NR-NR); 8-year OS rate was 80.8%. Median modified PFS was 9.4 months (95% CI 6.7-11.6 months) for pembrolizumab and 3.8 months (2.9-4.3 months) for ipilimumab [HR, 0.64 (95% CI 0.54-0.75)]. Among patients who received second-course pembrolizumab, median modified PFS from start of second course was 51.8 months (95% CI 11.0 months-NR); 6-year modified PFS was 49.2%. Median melanoma-specific survival was 51.9 months (95% CI 30.0-114.7 months) for pembrolizumab and 17.2 months (13.9-25.9 months) for ipilimumab [HR, 0.66 (95% CI 0.55-0.81)]. Conclusions: These results confirm that pembrolizumab provides long-term survival benefits in advanced melanoma, supporting it as a standard of care in this setting.

Original languageEnglish
JournalAnnals of Oncology
DOIs
StateAccepted/In press - 2024
Externally publishedYes

Keywords

  • immunotherapy
  • melanoma
  • pembrolizumab
  • phase III
  • programmed cell death protein 1

Fingerprint

Dive into the research topics of 'Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study'. Together they form a unique fingerprint.

Cite this