Five-Year Follow-Up of POLARIS-01 Phase II Trial: Toripalimab as Salvage Monotherapy in Chinese Patients With Advanced Melanoma
Mené en Chine sur 128 patients atteints d'un mélanome de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du toripalimab en traitement de sauvetage
Background: To investigate the efficacy and toxicity after long-term follow-up of anti-PD-1 antibody in advanced melanoma with predominantly acral and mucosal subtypes. Methods and Patients: In the POLARIS-01 phase II trial, 128 Chinese patients with advanced melanoma refractory to standard therapy received toripalimab until disease progression or unacceptable toxicity for
≤
2 years. For those who progressed after discontinuation due to 2-year treatment completion, rechallenge was allowed. The primary objectives were safety and overall response rate (ORR). Results: As of February 8, 2021, ORR was 17.3% (95% CI: 11.2-25.0) evaluated by the independent radiologic review committee. The median overall survival (OS) for patients with known melanoma subtypes was 16.3 m for acral, 41.5 m for nonacral cutaneous, and 10.3 m for mucosal melanoma. Thereafter, the evaluation was continued by investigators. As of November 4, 2022, 5 years after the last enrollment, median duration of response was 15.6 months (range, 3.7-64.5+), median progression-free survival (PFS) was 3.5 months (95% CI, 2.2-5.3), and 60-month OS rate was 28.5% (95% CI: 20.2-37.2). Thirteen patients completed a 2-year treatment of toripalimab, with the subtypes of acral (2/13), non-acral cutaneous (4/13), mucosal (3/13) and unknown primary (4/13). Five patients were rechallenged. Four of them, all of whom were non-mucosal, completed the rechallenge course of 2 years with PFS
≥
24 months. Conclusions: This is the largest prospective anti-PD-1 trial with mature data in advanced melanoma in China. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma who had failed in standard therapy. Immunotherapy seems less efficacious for long-term responders with mucosal primaries as rechallenge therapy.