De Ruysscher Dirk, Ramalingam Suresh, Urbanic James, Gerber David E, Tan Daniel S W, Cai Junliang, Li Ang, Peters Solange
Department of Radiation Oncology (Maastro), Maastricht University Medical Center, GROW School for Oncology and Developmental Biology, The Netherlands.
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.
Clin Lung Cancer. 2022 May;23(3):e264-e268. doi: 10.1016/j.cllc.2021.07.005. Epub 2021 Jul 19.
The 5 year survival rate for patients with locally advanced non-small-cell lung cancer (NSCLC) not amenable for definitive resection with historical standard-of-care concurrent chemoradiotherapy (cCRT) ranges from 15% to 32%. cCRT primes anti-tumor immunity and also upregulates programmed death ligand-1 (PD-L1), providing a rationale for combining an immune checkpoint inhibitor with cCRT to improve outcomes. In the PACIFIC trial, consolidation therapy with the PD-L1 inhibitor durvalumab improved progression-free survival (PFS) and overall survival (OS) vs. placebo in patients with stage III NSCLC who did not have disease progression after cCRT. CheckMate73L (NCT04026412), a randomized phase 3 study, evaluates the efficacy of nivolumab plus cCRT followed by nivolumab with or without ipilimumab vs. cCRT followed by durvalumab for untreated, stage III NSCLC.
Patients with untreated, stage III NSCLC will be randomized 1:1:1 to nivolumab plus cCRT followed by nivolumab in combination with ipilimumab (Arm A) or nivolumab alone (Arm B); or cCRT followed by durvalumab (Arm C). Primary endpoints are PFS and OS (Arm A vs. Arm C). Secondary endpoints include additional analyses of PFS and OS (Arm A vs. Arm B; Arm B vs. Arm C), as well as objective response rate, complete response rate, time to response, duration of response, time to death or distant metastases, and safety and tolerability. Recruitment began on August 20, 2019, and the estimated primary completion date is October 17, 2022.
对于无法进行根治性切除的局部晚期非小细胞肺癌（NSCLC）患者，采用历史标准的同步放化疗（cCRT）治疗，其5年生存率在15%至32%之间。cCRT可激发抗肿瘤免疫，还能上调程序性死亡配体-1（PD-L1），这为将免疫检查点抑制剂与cCRT联合使用以改善疗效提供了理论依据。在PACIFIC试验中，对于接受cCRT后未出现疾病进展的III期NSCLC患者，使用PD-L1抑制剂度伐利尤单抗进行巩固治疗，与安慰剂相比，可改善无进展生存期（PFS）和总生存期（OS）。CheckMate73L（NCT04026412）是一项随机3期研究，评估纳武利尤单抗联合cCRT，随后使用纳武利尤单抗加或不加伊匹木单抗，与cCRT后使用度伐利尤单抗相比，治疗未经治疗的III期NSCLC的疗效。
未经治疗的III期NSCLC患者将按1:1:1随机分组，分别接受纳武利尤单抗联合cCRT，随后使用纳武利尤单抗联合伊匹木单抗（A组）或单独使用纳武利尤单抗（B组）；或cCRT后使用度伐利尤单抗（C组）。主要终点是PFS和OS（A组与C组）。次要终点包括对PFS和OS的额外分析（A组与B组；B组与C组），以及客观缓解率、完全缓解率、缓解时间、缓解持续时间、死亡或远处转移时间，以及安全性和耐受性。招募工作于2019年8月20日开始，预计主要完成日期为2022年10月17日。
