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Preclinical and clinical evidence suggests that radiotherapy may act synergistically with immune checkpoint inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an open-label, single-arm, phase II study of atezolizumab plus stereotactic radiosurgery (SRS) in metastatic TNBC patients with brain metastases. The primary endpoint was progression-free survival (PFS) according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) bi-compartmental model. Secondary endpoints included extracranial objective response rate, overall survival (OS), and safety and tolerability. A safety run-in analysis for dose-limiting toxicity (DLT) was performed after the first 6 patients were enrolled and completed the assessment period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six patients were enrolled into the safety run-in phase between May 11, 2018 and October 24, 2019. No DLTs were observed, but the study was closed early due to slow accrual. Patients received a median of 2 atezolizumab cycles (range: 2\u201416), and SRS was administered to all 6 patients. Treatment-related adverse events (TRAEs) occurred in 4 participants (66.7%); all events were grade 2. The median bi-compartmental PFS was 1.3\u00a0months (95% confidence interval (CI): 0.95 \u2013 NA) and the median OS was 9.7\u00a0months (95% CI: 3.6 \u2013 NA). The best observed response by RECIST 1.1 criteria was stable disease\u2009\u2265\u200924\u00a0weeks in one participant (16.7%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Concurrent SRS with atezolizumab was feasible in TNBC patients with brain metastases. However, disease outcomes were poor, and the development of effective therapies for these patients remains a significant unmet medical need.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registry Number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\" ext-link-type=\"uri\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      NCT03483012.\n                    <\/jats:p>\n                    <jats:p>Trial Open to Accrual: 05\/01\/2018.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10549-026-07932-6","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T08:02:47Z","timestamp":1772870567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A phase II study of atezolizumab in combination with stereotactic radiation for patients with triple-negative breast cancer and brain metastasis"],"prefix":"10.1007","volume":"216","clinical-trial-number":[{"clinical-trial-number":"nct03483012","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Antonio","family":"Giordano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayal A.","family":"Aizer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabihah","family":"Tayob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Pereslete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Schoenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Pablo","family":"Leone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raechel","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy K.","family":"Erick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica L.","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Winer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Krop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Tolaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2263-5413","authenticated-orcid":false,"given":"Nancy U.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"issue":"20","key":"7932_CR1","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1056\/NEJMra1001389","volume":"363","author":"WD Foulkes","year":"2010","unstructured":"Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. 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Ayal A. Aizer reports research funding from Varian and NH TherAguix. Jonathan D. Schoenfeld reports research support paid to their institution from Merck, Bristol-Myers Squibb, Regeneron, Debiopharm, Siemens, and EMD Serono; consulting or participation on a scientific advisory board, and travel fees and payment for lectures from Aveta Biomics, Immunitas, IntraGel, LEK, SIRPant, Merck KGA, and EMD Serono; expert witness fees from Burns and White, Morgan and Morgan and Offutt Simmons Simonton; stock options from Immunitas and IntraGel. Jose Pablo Leone reports research funding from Kazia Therapeutics, AstraZeneca,\u00a0Lilly, and Roche; consulting honoraria from Minerva Biotechnologies.  Erica L. Mayer reports consulting for Lilly, AstraZeneca, Genentech\/Roche, Novartis, and Atkis. Nancy U. Lin reports institutional research support from Genentech, Pfizer, Merck, Seattle Genetics, Zion Pharmaceuticals, Olema Pharmaceuticals, and AstraZeneca; consulting honoraria from Seattle Genetics, Daiichi Sankyo, AstraZeneca, Olema Pharmaceuticals, Stemline\/Menarini, Artera Inc., Eisai,  Shorla Oncology,\u00a0Pfizer, and\u00a0Denali Therapeutics; royalties from Up to date (book); travel support from Olema, AstraZeneca, and Daiichi Sankyo.  Sara M. Tolaney reports consulting or advisory roles for Novartis, Pfizer\/Seagen, Merck, Eli Lilly, AstraZeneca, Genentech\/Roche, Eisai, Bristol Myers Squibb\/Systimmune, Daiichi Sankyo, Gilead, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini\/Stemline, Aadi Bio, Bayer, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson\/Ambrx, Bicycle Therapeutics, BeiGene Therapeutics, Mersana, Summitt Therapeutics, Avenzo Therapeutics, Aktis Oncology, Celcuity, Boehringer Ingelheim, Samsung Bioepis, Olema Pharmaceuticals, Tempus, Boundless Bio, and Denali Therapeutics; research funding from Genentech\/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, Seagen, OncoPep, Daiichi Sankyo, Menarini\/Stemline, Jazz Pharmaceuticals, and Olema Pharmaceuticals; and travel support from   Lilly, Gilead, Jazz Pharmaceuticals, Pfizer, Arvinas, and Roche.  All other authors report no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice Standards and the Declaration of Helsinki. Institutional review board (IRB) approval was obtained at Dana-Farber\/Harvard Cancer Center (DF\/HCC). The DF\/HCC Data and Safety Monitoring Committee (DSMC), which is composed of clinical specialists with experience in oncology and who had no direct relationship with the study, reviewed and monitored toxicity and accrual data from the study. Men and women of all races and ethnic groups were eligible for the trial. All participants provided written informed consent prior to the performance of any protocol specific procedures or assessments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All participants provided written informed consent prior to the performance of any protocol specific procedures or assessments.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}],"article-number":"24"}}