KEYNOTE-006 study: results of 10-year follow-up of pembrolizumab versus ipilimumab in advanced melanoma
Summary. Background. This study KEYNOTE-006 (NCT01866319) reports a 10-year follow-up of pembrolizumab versus ipilimumab in unresectable advanced melanoma. Materials and methods. Patients with unresectable stage III or IV melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg intravenously (iv) every 2 or 3 weeks for less than 2 years or to ipilimumab at a dose of 3 mg/kg IV every 3 weeks for four cycles. After completion of KEYNOTE-006, patients could cross over to the KEYNOTE-587 study (NCT03486873) for long-term follow-up. Eligible patients could receive a second course of pembrolizumab. The primary endpoint of the study was overall survival (OS), modified progression-free survival (PFS), modified PFS in the second course of pembrolizumab, and melanoma-specific survival as additional endpoints. Results. Of the 834 patients randomized to KEYNOTE-006 (556 participants received pembrolizumab and 278 — ipilimumab), 333 patients (39.9%) were eligible for KEYNOTE-587, but 211 of 333 patients crossed over to KEYNOTE-587 (25.3%) (159 patients received pembrolizumab, and 52 — ipilimumab). For patients who crossed over 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)). The 10-year survival rate was 34.0 and 23.6% in both groups, respectively. Among patients who completed pembrolizumab treatment for a time period greater than 94 weeks, the median OS from week 94 was not reached (NR) (NR; 95% CI NR–NR), with an 8-year OS rate of 80.8%. Median modified PFS was 9.4 months (95% CI 6.7–11.6 months) in the pembrolizumab group and 3.8 months (2.9–4.3 months) in the ipilimumab group (HR 0.64 (95% CI 0.54–0.75)). Among patients who received the second course of pembrolizumab, the median modified PFS from the start of the second course of treatment was 51.8 months (95% CI 11.0 months — NR), and the 6-year modified PFS rate was 49.2%. Median PFS was 51.9 months (95% CI 30.0–114.7 months) in the pembrolizumab group and 17.2 months (95% CI 13.9–25.9 months) in the ipilimumab group (HR 0.66 (95% CI 0.55–0.81)). Conclusions. The results show that pembrolizumab provides long-term survival benefits in advanced melanoma, supporting its role as a standard of care.
Leave a comment