Abstract
No direct comparison has been performed between different programmed cell death-1(PD-1)inhibitors for first-line treatment in patients with advanced non-small cell lung cancer(NSCLC).The feasibility of using PD-L1-expression-guided immunotherapy remains unknown.In this open-label,phase 2 study(NCT04252365),patients with advanced NSCLC without EGFR or ALK alterations were randomized(1∶1)to receive sintilimab or pembrolizumab monotherapy(PD-L1 expression ≥ 50％),or sintilimab or pembrolizumab plus platinum-based chemotherapy(PD-L1 expression＜50％).The sample size was cal-culated by optimal two-stage design.The primary endpoint was the objective response rate(ORR).The study included 71 patients(sintilimab arms,n=35;pembrolizumab arms,n=36)and met its primary endpoint,with a confirmed ORR of 51.4％(18/35)in the sintilimab arms.The confirmed ORR(95％confi-dence interval)was 46.2％(19.2％,74.9％)and 42.9％(17.7％,71.1％)for patients treated with sintilimab and pembrolizumab monotherapy;and 54.5％(32.2％,75.6％)and 45.4％(24.4％,67.8％)for those treated with sintilimab-and pembrolizumab-based combination therapies.The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination ther-apies.The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies.Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase Ⅲ studies.However,the incidence of rash was higher with sintilimab than pembrolizumab monotherapy.This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC.Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.
基金项目
Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer(2017B030314120)
Guangdong Provincial People's Hospital Scientific Research Funds for Leading Medical Talents in Guangdong Province(KJ012019426)
National Natural Science Foundation of China(82072562)
National Natural Science Foundation of China(82202997)
China Postdoctoral Science Foundation(2021M701422)
High-Level Hospital Construction Project(DFJH201810)
NETL
NSTL
万方数据