{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T02:14:55Z","timestamp":1782008095927,"version":"3.54.5"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"14","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,5,10]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Anti\u2013vascular endothelial growth factor therapy enhances PD-1 inhibitor activity in preclinical models and has been used to treat perilesional cerebral edema and radiation necrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              We conducted a two-institution phase II trial of bevacizumab and pembrolizumab in patients with untreated melanoma brain metastasis (MBM) (ClinicalTrials.gov identifier:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT02681549\">NCT02681549<\/jats:ext-link>\n              ). Patients were anti\u2013PD-(L)-1\u2013na\u00efve, and had \u2265one asymptomatic, nonhemorrhagic 5-20 mm MBM, not requiring immediate local therapy or steroids.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>Thirty-seven patients received four doses of bevacizumab and pembrolizumab every 3 weeks followed by up to 2 years of pembrolizumab. The brain metastasis response rate (primary end point) was 54.1% (95% CI, 36.9 to 70.5). The extracranial response rate was 56.3% (95% CI, 37.7 to 73.6). Median intracranial progression-free survival was 2.2 years (95% CI, 0.41 to not reached [NR]). Median overall survival (OS) was 4.3 years (95% CI, 1.6 to NR). Four-year OS rate was 51.6%. Grade 3 treatment-related adverse event rates from bevacizumab and pembrolizumab were 10.8% and 18.9%, respectively. Higher pretreatment vessel density in metastatic tumors and smaller on-therapy increases in circulating angiopoietin-2 were associated with response.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Pembrolizumab with bevacizumab was well tolerated and demonstrated substantial activity in patients with untreated MBM with promising OS, justifying further evaluation of this regimen.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-24-02219","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T21:00:08Z","timestamp":1741294808000},"page":"1685-1694","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain 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