Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase 3 KEYNOTE-006 study
Mené sur 834 patients atteints d'un mélanome non résécable de stade avancé (durée de suivi : 10 ans), cet essai de phase III compare l'efficacité, du point de vue de la survie globale, du pembrolizumab et de l'ipilimumab
Résumé en anglais
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 randomized (1:1:1) to pembrolizumab 10 mg/kg IV Q2W or Q3W for ≤2 years (pooled), or ipilimumab 3 mg/kg IV Q3W 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 end point was OS. Modified progression-free survival (PFS; censored at date last known alive), modified PFS on second-course pembrolizumab, and melanoma-specific survival (MSS) were exploratory.
Results: Of 834 patients randomized 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 cutoff for KEYNOTE-587 (May 1, 2024) was 123.7 months (range, 122.0-127.3). Median OS was 32.7 months (95% CI, 24.5-41.6) for pembrolizumab and 15.9 months (13.3-22.0) for ipilimumab (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) for pembrolizumab and 3.8 months (2.9-4.3) 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-NR); 6-year modified PFS was 49.2%. Median MSS was 51.9 months (95% CI, 30.0-114.7) for pembrolizumab and 17.2 months (13.9-25.9) 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.
