Rudin C.M.Awad M.M.Navarro A.Gottfried M.Peters S.Csoszi T.Cheema P.K.Rodriguez-Abreu D.Wollner M.CHIH-HSIN YANGMazieres J.Orlandi F.J.Luft A.G?m?? M.Kato T.Kalemkerian G.P.Luo Y.Ebiana V.Pietanza M.C.Kim H.R.KEYNOTE-604 Investigators2021-04-232021-04-2320200732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85088260697&doi=10.1200%2fJCO.20.00793&partnerID=40&md5=2c9b3e7a2db16910092fb26231087bb4https://scholars.lib.ntu.edu.tw/handle/123456789/557708Purpose: Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC. Methods: Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP. Primary end points were progression-free survival (PFS; RECIST version 1.1, blinded central review) and overall survival (OS) in the intention-to-treat population. Objective response rate (ORR) and duration of response were secondary end points. Prespecified efficacy boundaries were one-sided P = .0048 for PFS and .0128 for OS. Results: Of the 453 participants, 228 were randomly assigned to pembrolizumab plus EP and 225 to placebo plus EP. Pembrolizumab plus EP significantly improved PFS (hazard ratio [HR], 0.75; 95% CI, 0.61 to 0.91; P=.0023). Twelve-month PFS estimates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP. Although pembrolizumab plus EP prolonged OS, the significance threshold was not met (HR, 0.80; 95% CI, 0.64 to 0.98; P = .0164). Twenty-four-month OS estimates were 22.5% and 11.2%, respectively. ORR was 70.6% in the pembrolizumab plus EP group and 61.8% in the placebo plus EP group; the estimated proportion of responders remaining in response at 12 months was 19.3% and 3.3%, respectively. In the pembrolizumab plus EP and placebo plus EP groups, respectively, any-cause adverse events were grade 3-4 in 76.7% and 74.9%, grade 5 in 6.3% and 5.4%, and led to discontinuation of any drug in 14.8% and 6.3%. Conclusion: Pembrolizumab plus EP significantly improved PFS compared with placebo plus EP as first-line therapy for patients with ES-SCLC. No unexpected toxicities were seen with pembrolizumab plus EP. These data support the benefit of pembrolizumab in ES-SCLC. ? 2020 by American Society of Clinical Oncology.[SDGs]SDG3carboplatin; cisplatin; etoposide; lactate dehydrogenase; pembrolizumab; programmed death 1 ligand 1; antineoplastic agent; etoposide; monoclonal antibody; pembrolizumab; platinum; adult; aged; alopecia; anemia; area under the curve; Article; asthenia; backache; brain metastasis; cancer combination chemotherapy; cancer growth; cancer immunotherapy; cancer mortality; cancer patient; cancer survival; constipation; controlled study; coughing; decreased appetite; diarrhea; dizziness; double blind procedure; drug efficacy; drug withdrawal; fatigue; female; fever; headache; human; hyperthyroidism; hyponatremia; hypothyroidism; immunopathology; infusion related reaction; insomnia; intention to treat analysis; leukopenia; major clinical study; male; multiple cycle treatment; nausea; neutropenia; overall survival; peripheral edema; phase 3 clinical trial; plasma concentration-time curve; pneumonia; priority journal; progression free survival; pruritus; randomized controlled trial; rash; side effect; small cell lung cancer; thrombocytopenia; treatment duration; treatment response; vomiting; cancer staging; clinical trial; lung tumor; mortality; multicenter study; small cell lung cancer; survival analysis; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Etoposide; Female; Humans; Lung Neoplasms; Male; Neoplasm Staging; Platinum; Small Cell Lung Carcinoma; Survival Analysisjournal article10.1200/JCO.20.00793324689562-s2.0-85088260697