Publication date: Sep 15, 2024

Pembrolizumab significantly improved overall survival (OS) versus ipilimumab for unresectable advanced melanoma in KEYNOTE-006 (NCT01866319); 10-year follow-up data are presented. 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. 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)]. These results confirm that pembrolizumab provides long-term survival benefits in advanced melanoma, supporting it as a standard of care in this setting.

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