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First-line pembrolizumab plus chemotherapy versus chemotherapy in patients with advanced esophageal cancer: Chinese subgroup analysis of KEYNOTE-590.

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/m2 Q3W [d1; 6 doses] + 5-FU 800 mg/m2 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.