When to stop immunotherapy for advanced melanoma: the emulated target trials

作者：Mathilde Amiot, Laurent Mortier, Stéphane Dalle, O. Dereure, S. Dalac, Caroline Dutriaux, M.‐T. Leccia, E. Maubec, Jean‐Philippe Arnault, Florence Brunet-Possenti, Julie De Quatrebarbes, F. Granel‐Brocard, Caroline Gaudy‐Marqueste, Cécile Pagès, Pierre‐Emmanuel Stoebner, Philippe Saïag, Thierry Lesimple, A. Dupuy, Délphine Legoupil, Henri Montaudié, Bastien Oriano, Célèste Lebbé, Raphaël Porcher · 发表于：EClinicalMedicine · 年份：2024 · DOI：10.1016/j.eclinm.2024.102960 · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Cutaneous Melanoma Detection and Management、Melanoma and MAPK Pathways

Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years. Prolonged follow-up of responders after treatment cessation shows sustained response and a low risk of relapse in the months following cessation. To date, the optimal duration of anti-PD-1 therapy for metastatic melanoma remains unestablished. The objective of this work was to evaluate the optimal duration of ICI administration. Methods: We emulated target trials using the cloning, weighting and censoring approach. Each emulation trial aimed to compare the effect of discontinuing versus continuing ICIs at a specific timepoint, among patients still under treatment and with disease control at that time. Patients were from MelBase between 2015 and 2021. Findings: 435 participants in the MelBase cohort were eligible and were included in the 6-month discontinuation emulated trial. The results showed significantly lower OS when treatment was discontinued, than when treatment was prolonged for at least three months. The 48-month survival difference was 37.8% (95% confidence interval [CI] 19.8-60.5), and the corresponding restricted mean survival time difference was 8.3 months (95% CI: 4.1-12.7). Neither the 12-month nor the 18-month discontinuation emulated trials showed evidence of benefit of either discontinu...