{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:41:31Z","timestamp":1791726091034,"version":"4.3.4"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1\/PD-L1 inhibitors. Bevacizumab (anti\u2013vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; 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\/NCT04677504\">NCT04677504<\/jats:ext-link>\n                      ). Patients were randomly assigned 1:1 to receive cycles of atezolizumab (1,200 mg) plus bevacizumab (15 mg\/kg) or atezolizumab plus placebo once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) plus gemcitabine (1,000 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; cisplatin plus gemcitabine [CisGem]) on days 1 and 8 once every 3 weeks for up to eight cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary end point was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n = 95) and mutation profiling (n = 102) on baseline tumor samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo arm (stratified hazard ratio [HR], 0.67 [95% CI, 0.46 to 0.95]). Median overall survival (OS) was 14.9 and 14.6 months in the bevacizumab and placebo arms, respectively (stratified HR, 0.97 [95% CI, 0.64 to 1.47]). The incidence of grade 3 or 4 adverse events was 74% in both arms. High\n                      <jats:italic>VEGFA<\/jats:italic>\n                      gene expression was associated with improved PFS (HR, 0.44 [95% CI, 0.23 to 0.83]) in the bevacizumab arm versus placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS. High\n                      <jats:italic>VEGFA<\/jats:italic>\n                      gene expression may represent a predictive biomarker of benefit from atezolizumab\/bevacizumab, warranting further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00337","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T15:59:17Z","timestamp":1729267157000},"page":"545-557","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":38,"title":["Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04677504","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-4082","authenticated-orcid":true,"given":"Teresa","family":"Macarulla","sequence":"first","affiliation":[{"name":"Vall d'Hebron University Hospital, Vall d'Hebr\u00f3n Institute of Oncology (VHIO), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenggang","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6979-5812","authenticated-orcid":true,"given":"Hong Jae","family":"Chon","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, Seongnam-Si, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6502-2612","authenticated-orcid":true,"given":"Joon Oh","family":"Park","sequence":"additional","affiliation":[{"name":"Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital, Seongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6919-1536","authenticated-orcid":true,"given":"Tiziana","family":"Pressiani","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-7522","authenticated-orcid":true,"given":"Daneng","family":"Li","sequence":"additional","affiliation":[{"name":"City of Hope National Comprehensive Cancer Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila","family":"Zhukova","sequence":"additional","affiliation":[{"name":"SBIH \u201cMoscow Clinical Scientific and Practical Center Named After A.S. Loginov\u201d DHM, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7495-1528","authenticated-orcid":false,"given":"Andrew X.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiahui International Cancer Center, Jiahui Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-7393","authenticated-orcid":true,"given":"Ming-Huang","family":"Chen","sequence":"additional","affiliation":[{"name":"Taipei Veterans General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-5709","authenticated-orcid":true,"given":"Stephen P.","family":"Hack","sequence":"additional","affiliation":[{"name":"Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1477-8991","authenticated-orcid":true,"given":"Stephanie","family":"Wu","sequence":"additional","affiliation":[{"name":"Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangnan","family":"Guan","sequence":"additional","affiliation":[{"name":"Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Lu","sequence":"additional","affiliation":[{"name":"Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-9786","authenticated-orcid":true,"given":"Yulei","family":"Wang","sequence":"additional","affiliation":[{"name":"Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9053-3841","authenticated-orcid":true,"given":"Anthony B.","family":"El-Khoueiry","sequence":"additional","affiliation":[{"name":"USC Norris Comprehensive Cancer Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00153-7"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0310-z"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32803"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.4_suppl.LBA490"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00409-5"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00139-4"},{"key":"e_1_3_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.007"},{"key":"e_1_3_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30157-1"},{"key":"e_1_3_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30109-1"},{"key":"e_1_3_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.05.010"},{"key":"e_1_3_10_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00741-4"},{"key":"e_1_3_10_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00770-1"},{"key":"e_1_3_10_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI152670"},{"key":"e_1_3_10_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33013"},{"key":"e_1_3_10_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1312"},{"key":"e_1_3_10_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200015"},{"key":"e_1_3_10_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00727-4"},{"key":"e_1_3_10_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2021.1881479"},{"key":"e_1_3_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604129"},{"key":"e_1_3_10_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.598877"},{"key":"e_1_3_10_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_3_10_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.030"},{"key":"e_1_3_10_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/17588359211036544"},{"key":"e_1_3_10_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716948"},{"key":"e_1_3_10_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq057"},{"key":"e_1_3_10_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003118"},{"key":"e_1_3_10_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_10_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1349-1"},{"key":"e_1_3_10_31_2","unstructured":"U.S. Department of Health and Human Services: Common terminology criteria for adverse events (CTCAE) Version 5.0. 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