Atezolizumab Plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: a Multicenter, Open-label, Single-arm Phase 2 Study
Mené sur 43 patients atteints d'un mélanome muqueux (durée médiane de suivi : 13,4 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement de première ligne combinant atézolizumab et bévacizumab
Background: Anti-programed cell death-1 monotherapy is part of standard therapy for cutaneous melanoma but has low efficacy in mucosal melanoma. We evaluated the efficacy and safety of atezolizumab plus bevacizumab as first-line therapy for advanced mucosal melanoma. Patients and methods: This multicenter, open-label, single-arm, phase II study utilized a Simon’s two-stage design. Atezolizumab (fixed-dose, 1200 mg) and bevacizumab (7.5 mg/kg) were administered by intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR), determined per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety with adverse events summarized using NCI-CTCAE v5.0. Results: Overall, 43 patients were enrolled, including 20 (46.5%) with unresectable and 23 (53.5%) with metastatic mucosal melanoma. Median follow-up was 13.4 months at data cut-off (July 30, 2021). Forty patients were evaluable for response: ORR was 45.0% (95% confidence interval [CI], 29.3%–61.5%) (one complete response, 17 partial responses). Median PFS was 8.2 months (95% CI, 2.7–9.6); 6- and 12-month PFS rates were 53.4% (95% CI, 36.6%–67.6%) and 28.1% (95% CI, 14.2%–43.9%), respectively. Median OS was not reached (NR) (95% CI, 14.4–NR). Six- and 12-month OS rates were 92.5% (95% CI, 78.5%–97.5%) and 76.0% (95% CI, 57.1%–87.5%), respectively. Median DOR was 12.5 months (95% CI, 5.5–NR). Overall, 90.7% (39/43) of patients experienced treatment-related adverse events; 25.6% (11/43) experienced grade ≥3 events. Conclusion: Atezolizumab in combination with bevacizumab showed promising efficacy and manageable safety in patients with advanced mucosal melanoma.