Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
Peking Union Medical College Hospital, Beijing, China.
Int J Cancer. 2021 May 1;148(9):2313-2320. doi: 10.1002/ijc.33399. Epub 2020 Dec 9.
In the global KEYNOTE-042 study (Clinicaltrials.gov, NCT02220894), pembrolizumab significantly improved overall survival (OS) vs chemotherapy in patients with previously untreated programmed death ligand 1 (PD-L1)-positive locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. We present results from patients in KEYNOTE-042 enrolled from China in the global or extension study (NCT03850444; protocol identical to global study). Patients were randomized 1:1 (stratified by ECOG performance status 0 vs 1, squamous vs nonsquamous histology and PD-L1 tumor proportion score [TPS] ≥50% vs 1%-49%) to 35 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) or investigator's choice of 4 to 6 cycles of carboplatin plus paclitaxel or pemetrexed Q3W with optional pemetrexed maintenance for nonsquamous tumors. Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20% or ≥1%. Two hundred sixty-two patients (pembrolizumab, n = 128; chemotherapy, n = 134) were enrolled from China. At data cutoff (February 21, 2020; median follow-up, 33.0 [range, 25.6-41.9] months), pembrolizumab was shown to improve OS vs chemotherapy in patients with PD-L1 TPS ≥50% (hazard ratio [95% CI], 0.63 [0.43-0.94]), TPS ≥20% (0.66 [0.47-0.92]) and TPS ≥1% (0.67 [0.50-0.89]). Grade 3 to 5 treatment-related adverse events occurred less frequently with pembrolizumab vs chemotherapy (19.5% vs 68.8%). In 22 patients who completed 35 cycles of pembrolizumab, objective response rate was 77.3% and median duration of response was 27.6 months. Consistent with the global KEYNOTE-042 study, pembrolizumab improved OS vs chemotherapy in this study of Chinese patients with locally advanced/metastatic NSCLC and PD-L1 TPS ≥1%, supporting first-line pembrolizumab monotherapy for PD-L1-positive advanced/metastatic NSCLC in China.
在全球 KEYNOTE-042 研究（Clinicaltrials.gov，NCT02220894）中，与化疗相比， pembrolizumab 显著改善了未经治疗的程序性死亡配体 1（PD-L1）阳性局部晚期/转移性非小细胞肺癌（NSCLC）患者的总生存期（OS），这些患者没有 EGFR/ALK 改变。我们报告了来自中国患者的 KEYNOTE-042 全球或扩展研究（NCT03850444；方案与全球研究相同）的结果。患者按 1:1 随机分配（按 ECOG 表现状态 0 与 1、鳞状与非鳞状组织学以及 PD-L1 肿瘤比例评分 [TPS] ≥50%与 1%-49%分层），接受 35 个周期的 pembrolizumab 200mg 每 3 周（Q3W）或研究者选择的 4 至 6 个周期的卡铂加紫杉醇或培美曲塞 Q3W，非鳞状肿瘤可选择培美曲塞维持治疗。主要终点是 PD-L1 TPS ≥50%、≥20%或≥1%患者的 OS。从中国招募了 262 名患者（pembrolizumab，n = 128；化疗，n = 134）。在数据截止日期（2020 年 2 月 21 日；中位随访时间，33.0[范围，25.6-41.9]个月），与化疗相比，pembrolizumab 改善了 PD-L1 TPS ≥50%（风险比[95%CI]，0.63[0.43-0.94]）、TPS ≥20%（0.66[0.47-0.92]）和 TPS ≥1%（0.67[0.50-0.89]）患者的 OS。与化疗相比，pembrolizumab 发生 3 级至 5 级治疗相关不良事件的频率较低（19.5% vs 68.8%）。在完成 35 个周期 pembrolizumab 治疗的 22 名患者中，客观缓解率为 77.3%，中位缓解持续时间为 27.6 个月。与全球 KEYNOTE-042 研究一致，pembrolizumab 改善了中国局部晚期/转移性 NSCLC 和 PD-L1 TPS ≥1%患者的 OS，支持在中国将 pembrolizumab 单药作为 PD-L1 阳性晚期/转移性 NSCLC 的一线治疗。
