{"doi":"10.1056/nejmoa2034442","title":"Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma","abstract":"BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).","journal":"New England Journal of Medicine","year":2021,"id":145062,"datarank":7.044496919868664,"base_score":6.950814768442584,"endowment":6.950814768442584,"self_citation_contribution":1.0426222152663878,"citation_network_contribution":6.001874704602277,"self_endowment_contribution":1.0426222152663878,"citer_contribution":6.001874704602277,"corpus_percentile":null,"corpus_rank":null,"citation_count":1043,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02632409"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":614753,"name":"J. Alfred Witjes","orcid":"0000-0003-0059-3857","position":1,"is_corresponding":false},{"id":614754,"name":"Jürgen E. Gschwend","orcid":"0000-0003-1812-5103","position":2,"is_corresponding":false},{"id":614755,"name":"Michael Schenker","orcid":"0000-0003-2645-6391","position":3,"is_corresponding":false},{"id":614756,"name":"Begoña P. Valderrama","orcid":"0000-0003-0175-1263","position":4,"is_corresponding":false},{"id":226684,"name":"Yoshihiko Tomita","orcid":"0000-0002-7465-9591","position":5,"is_corresponding":false},{"id":614757,"name":"Aristotelis Bamias","orcid":"0000-0002-5996-7262","position":6,"is_corresponding":false},{"id":614758,"name":"Thierry Lebrét","orcid":"0000-0002-8664-3861","position":7,"is_corresponding":false},{"id":582191,"name":"Shahrokh F. Shariat","orcid":"0000-0002-6627-6179","position":8,"is_corresponding":false},{"id":614759,"name":"Se Hoon Park","orcid":"0000-0001-5084-9326","position":9,"is_corresponding":false},{"id":614760,"name":"Dingwei Ye","orcid":"0000-0002-0916-4218","position":10,"is_corresponding":false},{"id":614761,"name":"Mads Agerbæk","orcid":"0000-0003-3923-6136","position":11,"is_corresponding":false},{"id":614762,"name":"Deborah Enting","orcid":"0000-0001-7508-7540","position":12,"is_corresponding":false},{"id":614763,"name":"Ray McDermott","orcid":"0000-0002-8952-4315","position":13,"is_corresponding":false},{"id":614764,"name":"Pablo Gajate","orcid":"0000-0001-5156-7080","position":14,"is_corresponding":false},{"id":616634,"name":"Avivit Peer","orcid":null,"position":15,"is_corresponding":false},{"id":456370,"name":"Matthew I. Milowsky","orcid":"0000-0002-8965-8129","position":16,"is_corresponding":false},{"id":614765,"name":"А. К. Носов","orcid":"0000-0003-3850-7109","position":17,"is_corresponding":false},{"id":616635,"name":"João Neif Antonio","orcid":null,"position":18,"is_corresponding":false},{"id":614766,"name":"Krzysztof Tupikowski","orcid":"0000-0002-0958-7587","position":19,"is_corresponding":false},{"id":616636,"name":"Laurence Toms","orcid":null,"position":20,"is_corresponding":false},{"id":616637,"name":"Bruce S. 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