{"doi":"10.1056/nejmoa1801005","title":"Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer","abstract":"<h4>Background</h4>First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.<h4>Methods</h4>In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review.<h4>Results</h4>After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebo-combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P<0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group.<h4>Conclusions</h4>In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck; KEYNOTE-189 ClinicalTrials.gov number, NCT02578680 .).","journal":"New England Journal of Medicine","year":2018,"id":3015,"datarank":16.657055704805018,"base_score":8.783396232190894,"endowment":8.783396232190894,"self_citation_contribution":1.3175094348286343,"citation_network_contribution":15.339546269976385,"self_endowment_contribution":1.3175094348286343,"citer_contribution":15.339546269976385,"corpus_percentile":88.9,"corpus_rank":2038,"citation_count":6524,"citer_count":169,"citers_with_citation_signal":169,"citers_with_endowment":169,"datacite_reuse_total":0,"is_dataset":false,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2018-05-31","authors":[{"id":33754,"name":"Delvys Rodríguez-Abreu","orcid":null,"position":1,"is_corresponding":false},{"id":33755,"name":"Shirish Gadgeel","orcid":null,"position":2,"is_corresponding":false},{"id":33756,"name":"Emilio Esteban","orcid":"0000-0002-2980-5254","position":3,"is_corresponding":false},{"id":1544,"name":"Enriqueta Felip","orcid":"0000-0002-7620-0098","position":4,"is_corresponding":false},{"id":33757,"name":"Flávia De Angelis","orcid":null,"position":5,"is_corresponding":false},{"id":33758,"name":"Manuel Domine","orcid":null,"position":6,"is_corresponding":false},{"id":33759,"name":"Philip Clingan","orcid":null,"position":7,"is_corresponding":false},{"id":33760,"name":"Maximilian J. Hochmair","orcid":"0000-0002-8673-2450","position":8,"is_corresponding":false},{"id":33761,"name":"Steven F. Powell","orcid":null,"position":9,"is_corresponding":false},{"id":33762,"name":"Susanna Y.-S. Cheng","orcid":null,"position":10,"is_corresponding":false},{"id":33763,"name":"Helge G. Bischoff","orcid":null,"position":11,"is_corresponding":false},{"id":33764,"name":"Nir Peled","orcid":"0000-0003-3714-4377","position":12,"is_corresponding":false},{"id":33765,"name":"Francesco Grossi","orcid":"0000-0001-8412-3136","position":13,"is_corresponding":false},{"id":33766,"name":"Ross R. Jennens","orcid":null,"position":14,"is_corresponding":false},{"id":23851,"name":"Martin Reck","orcid":"0000-0002-5348-4462","position":15,"is_corresponding":false},{"id":33767,"name":"Rina Hui","orcid":"0000-0003-0696-7442","position":16,"is_corresponding":false},{"id":33768,"name":"Edward B. Garon","orcid":"0000-0001-7077-8801","position":17,"is_corresponding":false},{"id":33769,"name":"Michael Boyer","orcid":"0000-0002-0452-2987","position":18,"is_corresponding":false},{"id":33770,"name":"Belén Rubio-Viqueira","orcid":null,"position":19,"is_corresponding":false},{"id":32713,"name":"Silvia Novello","orcid":"0000-0001-7653-9748","position":20,"is_corresponding":false},{"id":33771,"name":"Takayasu Kurata","orcid":"0000-0003-4123-3567","position":21,"is_corresponding":false},{"id":33772,"name":"Jhanelle E. Gray","orcid":"0000-0003-1304-7062","position":22,"is_corresponding":false},{"id":33773,"name":"John Vida","orcid":null,"position":23,"is_corresponding":false},{"id":33774,"name":"Ziwen Wei","orcid":"0009-0000-5954-3825","position":24,"is_corresponding":false},{"id":24035,"name":"Jing Yang","orcid":"0000-0002-6640-5161","position":25,"is_corresponding":false},{"id":33775,"name":"Harry Raftopoulos","orcid":null,"position":26,"is_corresponding":false},{"id":33776,"name":"M. Catherine Pietanza","orcid":"0000-0002-5663-661X","position":27,"is_corresponding":false},{"id":33777,"name":"Marina C. Garassino","orcid":null,"position":28,"is_corresponding":false},{"id":33778,"name":"Delvys Rodríguez‐Abreu","orcid":"0000-0003-0506-1366","position":29,"is_corresponding":false},{"id":33779,"name":"Shirish M. Gadgeel","orcid":"0000-0001-5240-3811","position":30,"is_corresponding":false},{"id":33780,"name":"Manuel Dómine","orcid":"0000-0002-1128-434X","position":31,"is_corresponding":false},{"id":33781,"name":"Philip R. Clingan","orcid":null,"position":32,"is_corresponding":false},{"id":33782,"name":"Steven Powell","orcid":"0000-0002-5029-0048","position":33,"is_corresponding":false},{"id":33783,"name":"Susanna Y. Cheng","orcid":null,"position":34,"is_corresponding":false},{"id":33784,"name":"Helge Bischoff","orcid":"0000-0002-7693-0058","position":35,"is_corresponding":false},{"id":33785,"name":"Ross Jennens","orcid":"0000-0002-9872-997X","position":36,"is_corresponding":false},{"id":33786,"name":"Belén Rubio‐Viqueira","orcid":"0000-0001-5987-9214","position":37,"is_corresponding":false},{"id":33787,"name":"Marina Chiara Garassino","orcid":"0000-0002-3821-5598","position":38,"is_corresponding":false},{"id":33753,"name":"Leena Gandhi","orcid":"0000-0002-2398-9179","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}