{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:07:53Z","timestamp":1792976873615,"version":"4.5.0"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"\n Importance<\/jats:title>\n For patients with advanced non\u2013small cell lung cancer (NSCLC) and programmed cell death 1 ligand 1 (PD-L1) expression of 50% or higher, programmed cell death 1 protein or PD-L1 (PD-[L]1) inhibitor monotherapy is commonly used as first-line therapy; however, whether adding chemotherapy improves outcomes in this population remains unknown.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare overall survival (OS) and progression-free survival (PFS) associated with PD-(L)1 inhibitor monotherapy vs chemoimmunotherapy in treatment-naive patients with advanced NSCLC and high PD-L1 expression.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n PubMed, Embase, and major oncology conference proceedings were searched for phase 3 randomized clinical trials (RCTs) published before August 3, 2025.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Eligible studies were phase 3 RCTs that enrolled patients with untreated advanced NSCLC, evaluated PD-(L)1 inhibitor monotherapy or chemoimmunotherapy vs chemotherapy alone, and reported outcomes in patients with high PD-L1 expression.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n Hazard ratios (HRs) for OS and PFS were extracted from published studies and synthesized using inverse variance methods. Additional analyses included meta-regression, network meta-analysis, and reconstructed individual patient data from published Kaplan-Meier curves.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcome was OS; secondary outcome was PFS.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 24 trials including 5546 patients with PD-L1\u2013high NSCLC, 16 evaluated chemoimmunotherapy and 8 PD-(L)1 inhibitor monotherapy. Compared with chemotherapy, survival was improved by both chemoimmunotherapy (OS: HR, 0.63 [95% CI, 0.56-0.72];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; PFS: HR, 0.44 [95% CI, 0.39-0.49];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and PD-(L)1 inhibitor monotherapy (OS: HR, 0.74 [95% CI, 0.69-0.80];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; PFS: HR, 0.70 [95% CI, 0.65-0.76];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Tests for subgroup differences suggested improved benefit with chemoimmunotherapy compared to PD-(L)1 inhibitor monotherapy (OS: \u03c7\n 2<\/jats:sup>\n 1<\/jats:sub>\n \u2009=\u20094.1;\n P<\/jats:italic>\n \u2009=\u2009.04;\n \n I\n 2<\/jats:sup>\n <\/jats:italic>\n \u2009=\u200975.8%; PFS: \u03c7\n 2<\/jats:sup>\n 1<\/jats:sub>\n \u2009=\u200948.1;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001;\n \n I\n 2<\/jats:sup>\n <\/jats:italic>\n \u2009=\u200997.9%), consistent with meta-regression analyses (OS: HR, 0.85 [95% CI, 0.72-1.00];\n P<\/jats:italic>\n \u2009=\u2009.048; PFS: HR, 0.61 [95% CI, 0.50-0.75];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and network meta-analyses (OS: HR, 0.85 [95% CI, 0.73-0.99]; PFS: HR, 0.61 [95% CI, 0.50-0.75]). In the reconstructed individual patient data analysis, median OS was longer with chemoimmunotherapy (n\u2009=\u2009704 patients) compared to PD-(L)1 inhibitor monotherapy (n\u2009=\u20091706 patients) (29.2 months [95% CI, 25.2-35.4] vs 19.8 months [95% CI, 18.3-21.7]; HR, 0.74 [95% CI, 0.66-0.82];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Similarly, median PFS was significantly longer with chemoimmunotherapy (n\u2009=\u2009701 patients) compared to PD-(L)1 inhibitor monotherapy (n\u2009=\u20091706 patients) (11.3 months [95% CI, 10.3-13.5] vs 6.8 months [95% CI, 6.2-7.1]; HR, 0.67 [95% CI, 0.60-0.75];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this meta-analysis of phase 3 RCTs, chemoimmunotherapy was associated with significantly improved OS and PFS compared with PD-(L)1 inhibitor monotherapy in patients with advanced NSCLC and high PD-L1 expression. Prospective trials are needed to confirm these findings.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.1548","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:30:30Z","timestamp":1780587030000},"page":"753","source":"Crossref","is-referenced-by-count":5,"title":["PD-(L)1 Inhibitor Monotherapy vs Chemoimmunotherapy for Advanced NSCLC With High PD-L1 Expression"],"prefix":"10.1001","volume":"12","author":[{"given":"Alessandro","family":"Di Federico","sequence":"first","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Compagno","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mantuano","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Stumpo","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"De Giglio","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Pecci","sequence":"additional","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Department of Medicine and Surgery, University of Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao V.","family":"Alessi","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sperandi","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Melotti","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Gelsomino","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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