背景:目前,对于免疫治疗或靶向治疗失败的晚期黑色素瘤患者,目前缺乏治疗选择.最近的研究表明,pembrolizumab和lenvatinib联合治疗晚期黑色素瘤患者在免疫治疗过程中具有抗肿瘤活性。在这里,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)在该人群中的临床结局.
方法:这项法国多中心真实世界研究于2020年9月至2023年7月进行。主要终点是根据实体瘤的反应评估标准(1.1版)的客观反应率(ORR)。次要变量是治疗相关不良事件(TRAEs),无进展生存期(PFS),总生存期(OS),和响应持续时间(DOR)。
结果:在纳入的67例患者中(中位年龄,69年;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个完全(4.5%)和16个部分(23.9%)反应。中位数DOR为3.1(四分位数间距,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,分别。16例(24%)患者发生3-5级TRAE;常见的TRAE为疲劳(43.3%),恶心/呕吐(26.8%),腹泻(20.9%),和高血压(20.9%)。无治疗相关死亡发生。
结论:我们的真实世界研究表明,在具有不良预后因素的人群中,有有趣的缓解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选择,因为它没有得到美国食品和药物管理局或欧洲药品管理局的批准,并强调需要新的战略。
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.