{"doi":"10.1002/cncr.33142","title":"Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non–small cell lung cancer without tumor PD‐L1 expression: A pooled analysis of 3 randomized controlled trials","abstract":"BACKGROUND: Pembrolizumab plus platinum-based chemotherapy has demonstrated improved clinical outcomes over chemotherapy alone in patients with previously untreated advanced/metastatic non-small cell lung cancer (NSCLC), regardless of tumor programmed death ligand 1 (PD-L1) expression. This study pooled data from 3 randomized controlled trials to evaluate outcomes with pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced/metastatic NSCLC negative for PD-L1 (ie, a tumor proportion score < 1%). METHODS: Individual patient data were pooled from KEYNOTE-021 cohort G (nonsquamous; NCT02039674), KEYNOTE-189 (nonsquamous; NCT02578680 and NCT03950674), and KEYNOTE-407 (squamous; NCT02775435). Treatment comprised pembrolizumab plus chemotherapy (pemetrexed and platinum for nonsquamous histology and carboplatin and paclitaxel/nab-paclitaxel for squamous histology) or chemotherapy alone. Responses were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent, central review. No α was assigned to this descriptive, exploratory analysis. RESULTS: Four hundred forty-four of the 1328 patients (33.4%) who were enrolled across the 3 trials had PD-L1-negative tumors (256 on pembrolizumab plus chemotherapy [nonsquamous, n = 155; squamous, n = 94; other, n = 7] and 188 on chemotherapy alone [nonsquamous, n = 83; squamous, n = 99; other, n = 6]). The median time from randomization to the data cutoff was 28.0 months (range, 14.7-55.4 months). Pembrolizumab plus chemotherapy improved overall survival (OS; hazard ratio [HR], 0.63; 95% CI, 0.50-0.79) and progression-free survival (HR, 0.68; 95% CI, 0.56-0.83) over chemotherapy. Sixteen patients in the pembrolizumab plus chemotherapy arm completed 2 years of treatment; the objective response rate was 87.5% (95% CI, 61.7%-98.4%), and the 3-year OS rate was 100%. Adverse events (AEs) were experienced by 99.2% of the patients who received pembrolizumab plus chemotherapy and by 98.9% of the patients who received chemotherapy alone, with grade 3 or higher AEs occurring in 71.4% and 72.0%, respectively; immune-mediated AEs and infusion reactions were experienced by 29.0% and 12.4%, respectively. CONCLUSIONS: Pembrolizumab plus chemotherapy demonstrated response and survival improvements with manageable safety in comparison with chemotherapy alone in PD-L1-negative advanced/metastatic NSCLC, and it is a standard-of-care first-line therapy for patients with advanced NSCLC, regardless of PD-L1 expression. LAY SUMMARY: Some tumors produce a protein called programmed death ligand 1 (PD-L1), which interacts with the body's immune system and prevents an immune response against cancer. Antibody therapies such as pembrolizumab block interactions between tumor PD-L1 and the immune system and enable an immune response. Used alone, pembrolizumab provides benefit for patients with non-small cell lung cancer (NSCLC) tumors that produce PD-L1. However, when it is combined with chemotherapy, which can stimulate anticancer immune responses, pembrolizumab provides a benefit, regardless of tumor PD-L1 production. This article shows that among patients with NSCLC whose tumors produce no PD-L1, outcomes are better with pembrolizumab plus chemotherapy in comparison with chemotherapy alone.","journal":"Cancer","year":2020,"id":53868,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":111,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.938,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":272458,"name":"Corey J. Langer","orcid":"0000-0002-8483-6811","position":1,"is_corresponding":false},{"id":227930,"name":"Luis Paz‐Ares","orcid":"0000-0002-1947-3364","position":2,"is_corresponding":false},{"id":33778,"name":"Delvys Rodríguez‐Abreu","orcid":"0000-0003-0506-1366","position":3,"is_corresponding":false},{"id":263560,"name":"Balázs Halmos","orcid":"0000-0001-7548-8360","position":4,"is_corresponding":false},{"id":33787,"name":"Marina Chiara Garassino","orcid":"0000-0002-3821-5598","position":5,"is_corresponding":false},{"id":276655,"name":"Baerin Houghton","orcid":null,"position":6,"is_corresponding":false},{"id":33771,"name":"Takayasu Kurata","orcid":"0000-0003-4123-3567","position":7,"is_corresponding":false},{"id":275511,"name":"Ying Cheng","orcid":"0000-0001-9908-597X","position":8,"is_corresponding":false},{"id":276656,"name":"Jianxin Lin","orcid":null,"position":9,"is_corresponding":false},{"id":33776,"name":"M. Catherine Pietanza","orcid":"0000-0002-5663-661X","position":10,"is_corresponding":false},{"id":275512,"name":"Bilal Piperdi","orcid":"0000-0002-1315-3175","position":11,"is_corresponding":false},{"id":33779,"name":"Shirish M. Gadgeel","orcid":"0000-0001-5240-3811","position":12,"is_corresponding":false},{"id":275510,"name":"Hossein Borghaei","orcid":"0000-0002-2577-4454","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-18T20:45:25.145885Z","pmid":"32914866","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}