考比替尼联合阿特珠单抗用于既往接受抗程序性死亡-1治疗后进展的晚期BRAF野生型黑色素瘤患者的1b期研究。
Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAF wild-type melanoma progressing on prior anti-programmed death-1 therapy.
作者信息
Sandhu Shahneen, Atkinson Victoria, Cao Maria González, Medina Theresa, Rivas Ainara Soria, Menzies Alexander M, Caro Ivor, Roberts Louise, Song Yuyao, Yan Yibing, Guo Yu, Xue Cloris, Long Georgina V
机构信息
Department of Medical Oncology, Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
Department of Medical Oncology, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, and University of Queensland, Brisbane, Australia.
出版信息
Eur J Cancer. 2023 Jan;178:180-190. doi: 10.1016/j.ejca.2022.10.019. Epub 2022 Nov 2.
OBJECTIVE
To evaluate the efficacy and safety of cobimetinib plus atezolizumab in the treatment of patients with advanced BRAF wild-type melanoma who had progressed on prior anti‒programmed death-1 (PD-1) therapy.
PATIENTS AND METHODS
This phase 1b, open-label, international multicentre study enrolled 3 cohorts. Herein, we report on patients in cohorts A and B who had progressed on prior anti‒PD-1 therapy. Patients in cohort A received cobimetinib 60 mg once daily for 21 days followed by a 7-day break and concurrent intravenous atezolizumab 840 mg every 2 weeks. Patients in cohort B received the same dosing regimen as cohort A except for cycle 1 in which patients received cobimetinib only for the first 14 days prior to initiation of atezolizumab on cycle 1 day 15. Coprimary end-points were objective response rate and disease control rate. Secondary end-points were duration of response, progression free survival and overall survival.
RESULTS
Between 19th June 2017 and 12th December 2018, 103 patients were enrolled. Median follow-up was 6.9 months (interquartile range, 4.8-10.1 months); objective response rate was 14.6% and disease control rate was 38.8% (95% confidence interval, 29.39-48.94). The median duration of response, progression-free survival and overall survival was 12.7 months, 3.8 months and 14.7 months, respectively. The most common adverse events were diarrhoea (75/103; 72.8%), dermatitis acneiform (57/103; 55.3%) and nausea (52/103; 50.5%). Thirty-four patients (33.0%) died: 33 (91.7%) due to progressive disease and one (1%) due to treatment-related oesophagitis.
CONCLUSIONS
Combination therapy with cobimetinib and atezolizumab in patients with advanced BRAF wild-type melanoma with disease progression on or after prior anti‒PD-1 therapy demonstrated limited activity.
CLINICAL TRIAL REGISTRATION
This study is registered with ClinicalTrials.gov; NCT03178851.
目的
评估考比替尼联合阿特珠单抗治疗既往接受抗程序性死亡蛋白1（PD-1）治疗后病情进展的晚期BRAF野生型黑色素瘤患者的疗效和安全性。
患者与方法
这项1b期、开放标签、国际多中心研究纳入了3个队列。在此，我们报告队列A和队列B中既往接受抗PD-1治疗后病情进展的患者情况。队列A的患者接受考比替尼每日一次60mg，共21天，随后休息7天，并同时每2周静脉注射阿特珠单抗840mg。队列B的患者接受与队列A相同的给药方案，但在第1周期中，患者在第1周期第15天开始使用阿特珠单抗之前仅接受14天的考比替尼治疗。共同主要终点为客观缓解率和疾病控制率。次要终点为缓解持续时间、无进展生存期和总生存期。
结果
2017年6月19日至2018年12月12日期间，共纳入103例患者。中位随访时间为6.9个月（四分位间距，4.8 - 10.1个月）；客观缓解率为14.6%，疾病控制率为38.8%（95%置信区间，29.39 - 48.94）。中位缓解持续时间、无进展生存期和总生存期分别为12.7个月、3.8个月和14.7个月。最常见的不良事件为腹泻（75/103；72.8%）、痤疮样皮炎（57/103；55.3%）和恶心（52/103；50.5%）。34例患者（33.0%）死亡：33例（91.7%）死于疾病进展，1例（1%）死于与治疗相关的食管炎。
结论
考比替尼和阿特珠单抗联合治疗既往接受抗PD-1治疗时或之后病情进展的晚期BRAF野生型黑色素瘤患者，显示出有限的活性。
临床试验注册
本研究已在ClinicalTrials.gov注册；NCT03178851。
Zotero 插件