In a phase II trial (IMbrave151) reported in the Journal of Clinical Oncology, Macarulla et al found that atezolizumab/bevacizumab plus chemotherapy produced a “modest” improvement in progression-free survival vs atezolizumab/placebo plus chemotherapy in first-line treatment of patients with advanced biliary tract cancer. High VEGFA gene expression appeared to be associated with a more robust improvement in the atezolizumab/bevacizumab group.
Study Details
In the proof-of-concept double-blind trial, 162 patients from sites in 13 countries or regions, enrolled between February and September 2021, were randomly assigned to atezolizumab at 1,200 mg plus bevacizumab at 15 mg/kg (n = 79) or atezolizumab plus placebo (n = 83) once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin at 25 mg/m2 plus gemcitabine at 1,000 mg/m2 on days 1 and 8 once every 3 weeks for up to eight cycles.
The primary endpoint was progression-free survival. No formal hypothesis testing was performed to establish statistical significance level.
Key Findings
Median progression-free survival was 8.3 months (95% confidence interval [CI] = 6.8–10.6 months) in the atezolizumab/bevacizumab group vs 7.9 months (95% CI = 6.2–8.5 months) in the atezolizumab/placebo group (hazard ratio [HR] = 0.67, 95% CI = 0.46–0.95). Progression-free survival rates at 6 and 12 months were 78% vs 63% and 33% vs 20%, respectively.
Exploratory transcriptome analysis in 95 patients indicated a more robust improvement in progression-free survival among 25 patients in the atezolizumab/bevacizumab group vs 23 in the atezolizumab/placebo group with high VEGFA gene expression (HR = 0.44, 95% CI = 0.23–0.83).
Median overall survival was 14.9 months (95% CI = 11.6–18 months) in the atezolizumab/bevacizumab group vs 14.6 months (95% CI = 11.2 months to not estimable) in the atezolizumab/placebo group (stratified HR = 0.97, 95% CI = 0.64–1.47). Rates at 6 and 12 months were 92% vs 80.5% and 59% vs 54.6%.
Grade 3 or 4 adverse events occurred in 74% of patients in each group. Serious adverse events occurred in 46% of the atezolizumab/bevacizumab group vs 53% of the atezolizumab/placebo group. Adverse events led to discontinuation of any treatment component in 14% vs 11% of patients. Treatment-related death occurred in one patient (1.3%) vs two patients (2.5%).
The investigators concluded: “In unselected patients with advanced [biliary tract cancer], adding bevacizumab to atezolizumab plus [cisplatin/gemcitabine] improves [progression-free survival] but not [overall survival]. High VEGFA gene expression may represent a predictive biomarker of benefit from atezolizumab/bevacizumab, warranting further investigation.”
Anthony B. El-Khoueiry, MD, USC Norris Comprehensive Cancer Center, Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann-La Roche/Genentech. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
