Kojima T.Shah M.A.Muro K.Francois E.Adenis A.CHIH-HUNG HSUDoi T.Moriwaki T.Kim S.-B.Lee S.-H.Bennouna J.Kato K.Shen L.Enzinger P.Qin S.-K.Ferreira P.Chen J.Girotto G.de la Fouchardiere C.Senellart H.Al-Rajabi R.Lordick F.Wang R.Suryawanshi S.Bhagia P.Peter Kang S.Metges J.-P.KEYNOTE-181 Investigators2021-02-192021-02-1920200732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85096380116&doi=10.1200%2fJCO.20.01888&partnerID=40&md5=7746328aaa56c5b138c35f8995d3c9a2https://scholars.lib.ntu.edu.tw/handle/123456789/548994PURPOSE 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 a 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 5.0074). 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 5.0095) 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 5.0560) 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. ? 2020 by American Society of Clinical Oncology[SDGs]SDG3docetaxel; irinotecan; paclitaxel; pembrolizumab; programmed death 1 ligand 1; antineoplastic agent; CD274 protein, human; docetaxel; immunological antineoplastic agent; irinotecan; monoclonal antibody; paclitaxel; pembrolizumab; programmed death 1 ligand 1; adult; advanced cancer; adverse drug reaction; aged; alopecia; anemia; aspiration pneumonia; asthenia; cancer chemotherapy; cancer prognosis; comparative study; Conference Paper; controlled study; decreased appetite; demography; diarrhea; esophageal adenocarcinoma; esophageal squamous cell carcinoma; esophagus cancer; esophagus metastasis; fatigue; female; follow up; hemorrhagic shock; human; hypothyroidism; major clinical study; male; myocarditis; nausea; neutropenia; open study; overall survival; peripheral neuropathy; phase 3 clinical trial; pneumonia; priority journal; progression free survival; protein expression; randomized controlled trial; response evaluation criteria in solid tumors; sensory neuropathy; sepsis; squamous cell carcinoma; treatment response; vomiting; clinical trial; esophagus tumor; immunology; middle aged; multicenter study; pathology; survival rate; very elderly; young adult; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Docetaxel; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Irinotecan; Male; Middle Aged; Paclitaxel; Progression-Free Survival; Survival Rate; Young Adultconference paper10.1200/JCO.20.01888330269382-s2.0-85096380116