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Purpose: In the phase III KEYNOTE-181 study (NCT02564263) of patients with advanced esophageal cancer (EC), pembrolizumab monotherapy prolonged overall survival versus chemotherapy as second-line therapy in patients with programmed death ligand 1 combined positive score (CPS) ≥ 10. We present the results of the prespecified health-related quality-of-life (HRQoL) analyses of the squamous cell carcinoma (SCC), CPS ≥ 10, and CPS ≥ 10 SCC populations., Patients and Methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC questionnaire (OES18), and EuroQol 5-dimension questionnaire (EQ-5D). Data were analyzed in patients who received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment. Key analyses included baseline to week 9 least squares mean change in global health status/quality of life, functional or symptom subscales, and time to deterioration (≥ 10-point deterioration) for specific subscales., Results: The HRQoL population included 387 patients with SCC. Compliance and completion rates for all three questionnaires were similar in both treatment groups at baseline and week 9. No clinically meaningful differences in global health status/quality of life scores were observed between treatment groups from baseline to week 9 (least squares mean difference, 2.80; 95% CI, -1.48 to 7.08); patients in both treatment groups generally exhibited stable functioning and symptom scores of the QLQ-C30 and QLQ-OES18 from baseline to week 9. Time to deterioration for pain (hazard ratio [HR], 1.22; 95% CI, 0.79 to 1.89), reflux (HR, 2.38; 95% CI, 1.33 to 4.25), and dysphagia (HR, 1.53; 95% CI, 1.02 to 2.31) subscales were similar between treatment groups. These findings were generally similar in the CPS ≥ 10 (n = 218) and CPS ≥ 10 SCC (n = 166) subgroups., Conclusion: In patients with advanced EC, pembrolizumab monotherapy and chemotherapy maintained HRQoL in patients with SCC, CPS ≥ 10, and CPS ≥ 10 SCC., Competing Interests: Antoine AdenisHonoraria: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, Bristol Myers SquibbConsulting or Advisory Role: Bristol Myers Squibb, Merck, Merck SeronoResearch Funding: Bayer (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Amit S. KulkarniEmployment: MerckStock and Other Ownership Interests: Merck Gustavo C. GirottoConsulting or Advisory Role: MSDSpeakers' Bureau: MSDResearch Funding: MSD (Inst) Christelle de la FouchardiereHonoraria: Merck Serono, RocheConsulting or Advisory Role: Lilly, Bayer, Amgen, Bristol Myers Squibb, Servier, Roche¸ Pierre Fabre OncologyResearch Funding: Roche (Inst)Travel, Accommodations, Expenses: Roche, Celgene, Amgen, Bristol Myers Squibb, Servier, RocheOther Relationship: Incyte, MSD Hanneke W. M. van LaarhovenConsulting or Advisory Role: Nordic Pharma, Lilly, Bristol Myers Squibb, Servier, MSDResearch Funding: Bristol Myers Squibb (Inst), Bayer (Inst), Lilly (Inst), Nordic Pharma (Inst), MSD, Servier (Inst) Wasat MansoorHonoraria: BMS, ServierConsulting or Advisory Role: BMS, Servier Raed Al-RajabiHonoraria: AstraZeneca, BayerSpeakers' Bureau: Sirtex Josephine NorquistEmployment: MerckStock and Other Ownership Interests: Merck Mayur AmonkarEmployment: Merck Shailaja SuryawanshiEmployment: Merck Pooja BhagiaEmployment: Merck Jean-Philippe MetgesHonoraria: BMS, Bayer, MSDNo other potential conflicts of interest were reported.

Purpose: Patients with advanced esophageal cancer have a poor prognosis and limited treatment options after first-line chemotherapy., Patients and Methods: In this open-label, phase III study, we randomly assigned (1:1) 628 patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab 200 mg every 3 weeks for up to 2 years or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). Primary end points were overall survival (OS) in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10, in patients with squamous cell carcinoma, and in all patients (one-sided α 0.9%, 0.8%, and 0.8%, respectively)., Results: At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3 v 6.7 months; hazard ratio [HR], 0.69 [95% CI, 0.52 to 0.93]; P = .0074). Estimated 12-month OS rate was 43% (95% CI, 33.5% to 52.1%) with pembrolizumab versus 20% (95% CI, 13.5% to 28.3%) with chemotherapy. Median OS was 8.2 months versus 7.1 months (HR, 0.78 [95% CI, 0.63 to 0.96]; P = .0095) in patients with squamous cell carcinoma and 7.1 months versus 7.1 months (HR, 0.89 [95% CI, 0.75 to 1.05]; P = .0560) in all patients. Grade 3-5 treatment-related adverse events occurred in 18.2% of patients with pembrolizumab versus 40.9% in those who underwent chemotherapy., Conclusion: Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10, with fewer treatment-related adverse events.