Open AccessNivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer
Author(s) -
Zhou Yixin,
Zhang Yaqiong,
Guo Guifang,
Cai Xiuyu,
Yu Hui,
Cai Yanyu,
Zhang Bei,
Hong Shaodong,
Zhang Li
Publication year - 2020
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.14
Subject(s) - nivolumab , medicine , pembrolizumab , ipilimumab , hazard ratio , lung cancer , chemotherapy , oncology , progression free survival , gastroenterology , cancer , confidence interval , immunotherapy
Abstract Background Nivolumab plus ipilimumab (N‐I) or pembrolizumab (PEM) is associated with survival improvement as chemotherapy‐free, first‐line treatment for patients with advanced non‐small cell lung carcinoma (NSCLC) and positive programmed cell death ligand 1 (PD‐L1). However, no direct comparison data exist between these two regimens to inform clinical decisions. Therefore, we performed indirect comparison for N‐I versus PEM using frequentist methods. Results Three randomized trials (KEYNOTE‐024, KEYNOTE‐042, and CheckMate 227) involving 2372 patients were included. For patients with tumor PD‐L1 level of ≥1%, pooled meta‐analyses showed that both N‐I and PEM improved overall survival (OS) relative to chemotherapy (N‐I: hazard ratio [HR] 0.82, 95% CI 0.69‐0.97; PEM: HR 0.81, 95% CI 0.71‐0.93); whereas only N‐I significantly improved progression‐free survival (PFS) (N‐I: HR 0.79, 95% CI 0.65‐0.96; PEM: HR 1.07, 95% CI 0.94‐1.21). Neither N‐I nor PEM was associated with improved objective response rate (ORR) compared with chemotherapy (N‐I: relative risk [RR] 1.20, 95% CI 0.98‐1.46; PEM: RR 1.03, 95% CI 0.86‐1.23). Indirect comparisons showed that N‐I was associated with longer PFS than PEM (HR 0.77, 95% CI 0.62‐0.95). However, N‐I was not superior to PEM in terms of OS (HR 0.98, 95% CI 0.77‐1.24) and ORR (RR 1.17, 95% CI 0.89‐1.52). N‐I showed a less favorable toxicity profile relative to PEM (all grade adverse events: RR 1.28, 95% CI 1.17‐1.40). Conclusions N‐I and PEM provide comparable OS benefit for PD‐L1‐positive NSCLC. N‐I further improves PFS relative to PEM but at meaningful cost of toxicities.