{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:07:15Z","timestamp":1794017235398,"version":"4.8.0"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"Importance<\/jats:title>Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1\u2013positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)\/PD-L1 immunotherapy has not been extensively determined.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This phase 2 randomized clinical trial was conducted in 6 centers from August 2017 to June 2021.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients with metastatic TNBC were randomized to receive carboplatin area under the curve (AUC) 6 alone or with atezolizumab, 1200 mg, every 3 weeks until disease progression or unacceptable toxic effects with a 3-year duration of follow-up.<\/jats:p><\/jats:sec>Main Outcome and Measures<\/jats:title>The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). Other objectives included correlation of response with tumor PD-L1 levels, tumor-infiltrating lymphocytes (TILs), tumor DNA- and RNA-sequenced biomarkers, TNBC subtyping, and multiplex analyses of immune markers.<\/jats:p><\/jats:sec>Results<\/jats:title>All 106 patients with metastatic TNBC who were enrolled were female with a mean (range) age of 55 (27-79) years, of which 12 (19%) identified as African American\/Black, 1 (1%) as Asian, 73 (69%) as White, and 11 (10%) as unknown. Patients were randomized and received either carboplatin (n\u2009=\u200950) or carboplatin and atezolizumab (n\u2009=\u200956). The combination improved PFS (hazard ratio [HR], 0.66; 95% CI, 0.44-1.01; P<\/jats:italic>\u2009=\u2009.05) from a median of 2.2 to 4.1 months, increased ORR from 8.0% (95% CI, 3.2%-18.8%) to 30.4% (95% CI, 19.9%-43.3%), increased CBR at 6 months from 18.0% (95% CI, 9.8%-30.1%) to 37.5% (95% CI, 26.0%-50.6%), and improved OS (HR, 0.60; 95% CI, 0.37-0.96; P<\/jats:italic>\u2009=\u2009.03) from a median of 8.6 to 12.6 months. Subgroup analysis showed PD-L1\u2013positive tumors did not benefit more from adding atezolizumab (HR, 0.62; 95% CI, 0.23-1.65; P<\/jats:italic>\u2009=\u2009.35). Patients with high TILs (HR, 0.12; 95% CI, 0.30-0.50), high mutation burden (HR, 0.50; 95% CI, 0.23-1.06), and prior chemotherapy (HR, 0.59; 95% CI, 0.36-0.95) received greater benefit on the combination. Patients with obesity and patients with more than 125 mg\/dL on-treatment blood glucose levels were associated with better PFS (HR, 0.35; 95% CI, 0.10-1.80) on the combination. TNBC subtypes benefited from adding atezolizumab, except the luminal androgen receptor subtype.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial, the addition of atezolizumab to carboplatin significantly improved survival of patients with metastatic TNBC regardless of PD-L1 status. Further, lower risk of disease progression was associated with increased TILs, higher mutation burden, obesity, and uncontrolled blood glucose levels.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03206203<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.5424","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T16:01:39Z","timestamp":1702569699000},"page":"193","source":"Crossref","is-referenced-by-count":40,"title":["Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer"],"prefix":"10.1001","volume":"10","author":[{"given":"Brian D.","family":"Lehmann","sequence":"first","affiliation":[{"name":"Department of Medicine, Vanderbilt University, Nashville, Tennessee"},{"name":"Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana G.","family":"Abramson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University, Nashville, Tennessee"},{"name":"Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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