目前，对于免疫治疗或靶向治疗失败的晚期黑色素瘤患者缺乏治疗选择。最近的研究表明，派姆单抗和仑伐替尼联合治疗对接受免疫疗法进展的晚期黑色素瘤患者具有抗肿瘤活性。在此，我们报告了乐伐替尼和程序性细胞死亡蛋白 1 抑制剂 (PD-1) 联合治疗该人群的临床结果。这项法国多中心真实世界研究于 2020 年 9 月至 2023 年 7 月期间进行。主要终点是目标根据实体瘤疗效评估标准（1.1 版）的缓解率 (ORR)。次要变量是治疗相关不良事件 (TRAE)、无进展生存期 (PFS)、总生存期 (OS) 和缓解持续时间 (DOR)。 纳入的 67 名患者中（中位年龄 69 岁；中位随访时间，5.0 个月），85% 患有 IV-M1c 或 M1d 期疾病。总体 ORR 为 28.4%（95% CI，18%-41%），包括 3 例完全缓解（4.5%）和 16 例部分缓解（23.9%）。中位 DOR 为 3.1（四分位距，1.3-4.3）个月。中位 PFS 和 OS 分别为 3.1 (95% CI, 2.5-3.7) 和 9.8 (95% CI, 5.6-13.9) 个月。 16 名 (24%) 患者发生了 3-5 级 TRAE；常见的 TRAE 包括疲劳（43.3%）、恶心/呕吐（26.8%）、腹泻（20.9%）和高血压（20.9%）。没有发生与治疗相关的死亡。我们的现实世界研究表明，在预后因素较差的人群中，有有趣的反应率和可接受的安全性。我们的数据支持这种难治性黑色素瘤的治疗方案，因为它未经美国食品和药物管理局或欧洲药品管理局批准，并强调需要新的策略。© 作者 2024。由牛津大学出版社出版。

Currently, treatment options for patients with advanced melanoma who experience failed immunotherapy or targeted therapy are lacking. Recent studies suggest the antitumor activity of combined pembrolizumab and lenvatinib in patients with advanced melanoma progressing on immunotherapy. Herein, we report the clinical outcomes of combined lenvatinib and a programmed cell death protein-1 inhibitor (PD-1) in this population.This French multicenter real-world study was conducted between September 2020 and July 2023. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (version 1.1). Secondary variables were treatment-related adverse events (TRAEs), progression-free survival (PFS), overall survival (OS), and duration of response (DOR).Of the 67 patients included (median age, 69 years; median follow-up, 5.0 months), 85% had stage IV-M1c or M1d disease. The overall ORR was 28.4% (95% CI, 18%-41%), including 3 complete (4.5%) and 16 partial (23.9%) responses. Median DOR was 3.1 (interquartile range, 1.3-4.3) months. Median PFS and OS were 3.1 (95% CI, 2.5-3.7) and 9.8 (95% CI, 5.6-13.9) months, respectively. Grades 3-5 TRAEs occurred in 16 (24%) patients; common TRAEs were fatigue (43.3%), nausea/vomiting (26.8%), diarrhea (20.9%), and hypertension (20.9%). No treatment-related deaths occurred.Our real-world study demonstrates an interesting response rate and acceptable safety profile in a population with poor prognostic factors. Our data support this treatment option for refractory melanoma, as it is not approved by the Food and Drug Administration or European Medicines Agency, and highlight the need for new strategies.© The Author(s) 2024. Published by Oxford University Press.