{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T18:37:00Z","timestamp":1793558220532,"version":"4.5.0"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"\n Importance<\/jats:title>\n The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with\n ERBB2<\/jats:italic>\n -positive breast cancer and brain metastases.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with\n ERBB2<\/jats:italic>\n -positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n \n Patients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg\/m\n 2<\/jats:sup>\n , twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n The results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with\n ERBB2<\/jats:italic>\n -positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04582968<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.5791","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T11:32:10Z","timestamp":1704367930000},"page":"335","source":"Crossref","is-referenced-by-count":37,"title":["Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With\n ERBB2<\/i>\n -Positive Advanced Breast Cancer and Brain Metastases"],"prefix":"10.1001","volume":"10","author":[{"given":"Zhaozhi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"},{"name":"Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinli","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"},{"name":"Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Palmer","sequence":"additional","affiliation":[{"name":"The James Cancer Center at The Ohio State University, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"},{"name":"Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 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