2026-04-13T05:53:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/126992025-09-30T02:07:00Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Ren, Zhenggang author Chon, Hong Jae author Park, Joon Oh author Pressiani, Tiziana author Kim, Jin Won author Macarulla, Teresa author 2025-03-06T13:16:29Z 2025-03-06T13:16:29Z 2024 2025-02-10 Chemotherapy; Advanced biliary tract cancer; Biomarker Quimioteràpia; Càncer de les vies biliars Biomarcadors Quimioterapia; Cáncer de las vías biliares: Biomarcadores Purpose Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti–vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition. Patients and Methods This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; ClinicalTrials.gov identifier: NCT04677504). 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/m2) plus gemcitabine (1,000 mg/m2; 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. Results 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 VEGFA gene expression was associated with improved PFS (HR, 0.44 [95% CI, 0.23 to 0.83]) in the bevacizumab arm versus placebo. Conclusion In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS. High VEGFA gene expression may represent a predictive biomarker of benefit from atezolizumab/bevacizumab, warranting further investigation. This study was sponsored by F. Hoffmann-La Roche Ltd/Genentech, Inc. Conductes biliars - Càncer - Tractament Marcadors tumorals Quimioteràpia combinada Anticossos monoclonals - Ús terapèutic ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized Other subheadings::Other subheadings::/therapeutic use CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Biliary Tract Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales Otros calificadores::Otros calificadores::/uso terapéutico COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias del tracto biliar Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial