Multinational randomized phase 2 trial of atezolizumab plus chemotherapy with or without bevacizumab for advanced biliary tract cancer

Biliary tract cancers harbor an immunosuppressed tumor microenvironment and respond poorly to PD-(L)1 inhibitors given in monotherapy. The multinational randomized phase 2 IMbrave151 trial evaluated addition of bevacizumab to first-line atezolizumab plus chemotherapy for advanced biliary tract cancer (aBTC). All patients received up to eight cycles of cisplatin-gemcitabine chemotherapy. Patients were randomized to atezolizumab plus bevacizumab or atezolizumab plus placebo until disease progression or unacceptable toxicity. Addition of bevacizumab to atezolizumab plus chemotherapy was associated with significantly improved progression-free survival but not with signifcant improvement in overall survival. The incidence of grade 3 or 4 adverse events was 74% in both arms. High VEGFA gene expression was associated with improved PFS (11.0 versus 6.6 months; HR 0.44; 95% CI 0.23-0.83) and a trend of improved OS (17.2 versus 12.4 months; HR 0.65; 95% CI 0.31-1.31) with bevacizumab versus placebo. The authors conclude that in unselected patients with aBTC, adding bevacizumab to first-line atezolizumab plus chemotherapy modestly improved PFS but not OS. High VEGFA gene expression may be a predictive biomarker of benefit from addition of bevacizumab.