2026-04-17T11:54:53Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/126992025-09-30T02:07:00Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Ren, Zhenggang
author
Chon, Hong Jae
author
Park, Joon Oh
author
Pressiani, Tiziana
author
Kim, Jin Won
author
Macarulla, Teresa
2025-03-06T13:16:29Z2025-03-06T13:16:29Z20242025-02-10
Chemotherapy; Advanced biliary tract cancer; BiomarkerQuimioteràpia; Càncer de les vies biliars BiomarcadorsQuimioterapia; Cáncer de las vías biliares: BiomarcadoresPurpose
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.
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
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
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion