First-line pembrolizumab plus chemotherapy versus chemotherapy in patients with advanced esophageal cancer: Chinese subgroup analysis of KEYNOTE-590.
Authors: Zhigang Li, Yubei Sun, Feng Ye, Dong Ma, Xianli Yin, Wu Zhuang, Xianglin Yuan, Shukui Qin, Yiping Zhang, Kangsheng Gu, Kuaile Zhao, Juxiang Xiao, Ying Cheng, Yuxian Bai, Suxia Luo, Liwei Wang, Cailian Wang, Yi Cui, Lingling Mei, Lin Shen
Journal: Journal of Clinical Oncology (2021)

4049 Background: In the randomized, double-blind, placebo-controlled, multicenter, phase 3 KEYNOTE-590 study (NCT03189719), pembrolizumab + chemotherapy provided superior OS, PFS, and ORR versus chemotherapy with a manageable safety profile in patients with untreated locally advanced/unresectable or metastatic adenocarcinoma or esophageal squamous cell carcinoma (ESCC) or Siewert type 1 esophagogastric junction (EGJ) adenocarcinoma. We present results from the subgroup of patients enrolled in China. Methods: Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo Q3W for ≤35 cycles (̃2 years) + chemotherapy (cisplatin 80 mg/m 2 Q3W [d1; 6 doses] + 5-FU 800 mg/m 2 on d1-d5 Q3W). Randomization was stratified by region, histology, and ECOG performance status. Primary end points were OS in patients with ESCC PD-L1 combined positive score (CPS) ≥10 tumors and OS and PFS (RECIST v1.1; by investigator) in ESCC, PD-L1 CPS ≥10, and all patients; ORR (RECIST v1.1; by investigator) in all patients was the key secondary end point. Data cutoff was July 2, 2020. Results: Of 749 patients enrolled, 106 (14.2%) enrolled in China (51 in pembrolizumab + chemotherapy arm; 55 in chemotherapy arm); 88.7% were male and 49.1% had PD-L1 CPS ≥10. In Chinese patients, ECOG performance status 1 (81.1% vs 59.8%) and ESCC (98.1% vs 73.2%) were more prevalent than they were in all patients enrolled in the study. Additionally, in Chinese patients (pembrolizumab + chemotherapy vs chemotherapy), median OS was 10.5 months versus 8.0 months (HR, 0.51; 95% CI, 0.32-0.81), median PFS was 6.2 months versus 4.6 months (HR, 0.60; 95% CI, 0.39-0.92), ORR was 37.3% versus 20.0%, and median DOR (range) was 6.4 months (2.2+ to 18.9+) versus 4.0 months (1.5+ to 16.6+). Grade 3 or 4 treatment-related adverse events (TRAEs) were reported in 74.5% of patients in the pembrolizumab + chemotherapy arm and 66.7% in the chemotherapy arm; no grade 5 events were reported. Eight patients (15.7%) in the pembrolizumab + chemotherapy arm and 3 patients (5.6%) in the chemotherapy arm discontinued because of TRAEs. Immune-mediated AEs (defined for the safety profile of pembrolizumab as events with potentially treatment-related immunologic causes) were reported in 21.6% of patients in the pembrolizumab + chemotherapy arm and 13.0% in the chemotherapy arm; most were grade 1 or 2 and were manageable with interruption or discontinuation of study drug or standard medical therapy. Conclusions: In Chinese patients with advanced esophageal or EGJ cancer, pembrolizumab + chemotherapy improved OS, PFS, and ORR versus chemotherapy as first-line therapy, and safety was manageable. These findings were consistent with those in the global study population. Clinical trial information: NCT03189719.