Zhou Yixin, Zhang Yaqiong, Guo Guifang, Cai Xiuyu, Yu Hui, Cai Yanyu, Zhang Bei, Hong Shaodong, Zhang Li
State Key Laboratory of Oncology in South China, Guangzhou, China.
Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Clin Transl Med. 2020 Jan;10(1):107-115. doi: 10.1002/ctm2.14. Epub 2020 Apr 7.
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.
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).
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.
纳武利尤单抗联合伊匹木单抗（N-I）或帕博利珠单抗（PEM）作为晚期非小细胞肺癌（NSCLC）且程序性细胞死亡配体1（PD-L1）阳性患者的无化疗一线治疗方案，与生存改善相关。然而，这两种方案之间尚无直接比较数据来指导临床决策。因此，我们采用频率论方法对N-I与PEM进行间接比较。
纳入了三项涉及2372例患者的随机试验（KEYNOTE-024、KEYNOTE-042和CheckMate 227）。对于肿瘤PD-L1水平≥1%的患者，汇总的荟萃分析显示，相对于化疗，N-I和PEM均改善了总生存期（OS）（N-I：风险比[HR]0.82，95%置信区间0.69-0.97；PEM：HR 0.81，95%置信区间0.71-0.93）；而只有N-I显著改善了无进展生存期（PFS）（N-I：HR 0.79，95%置信区间0.65-0.96；PEM：HR 1.07，95%置信区间0.94-1.21）。与化疗相比，N-I和PEM均未显示客观缓解率（ORR）有所改善（N-I：相对风险[RR]1.20，95%置信区间0.98-1.46；PEM：RR 1.03，95%置信区间0.86-1.23）。间接比较显示，N-I与比PEM更长的PFS相关（HR 0.77，95%置信区间0.62-0.95）。然而，在OS（HR 0.98，95%置信区间0.77-1.24）和ORR（RR 1.17，95%置信区间0.89-1.52）方面，N-I并不优于PEM。相对于PEM，N-I的毒性特征较差（所有级别不良事件：RR 1.28，95%置信区间1.17-1.40）。
N-I和PEM为PD-L1阳性NSCLC患者提供了相当的OS获益。相对于PEM，N-I进一步改善了PFS，但毒性代价显著。
