Atezolizumab combined with bevacizumab alongside chemotherapy has demonstrated a modest improvement in progression-free survival (PFS) for patients with advanced biliary tract cancer (BTC). The findings come from the phase II IMbrave151 trial, recently published in the Journal of Clinical Oncology, and suggest a potential new first-line treatment option for this challenging cancer.
The double-blind trial, led by Macarulla et al., involved 162 patients across 13 countries, randomized to receive either atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo, every 3 weeks. All patients also received cisplatin (25 mg/m2) and gemcitabine (1000 mg/m2) for up to eight cycles. The primary endpoint was progression-free survival.
The results indicated a median PFS of 8.3 months (95% CI, 6.8-10.6 months) in the atezolizumab/bevacizumab arm compared to 7.9 months (95% CI, 6.2-8.5 months) in the atezolizumab/placebo arm (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, favoring the combination therapy.
Biomarker Potential
Exploratory transcriptome analysis revealed that patients with high VEGFA gene expression experienced a more pronounced improvement in PFS with the atezolizumab/bevacizumab combination (HR = 0.44, 95% CI = 0.23-0.83). This suggests that VEGFA expression could serve as a predictive biomarker for identifying patients most likely to benefit from this treatment approach.
Survival and Safety
Median overall survival (OS) was similar between the two groups, with 14.9 months (95% CI, 11.6-18 months) in the atezolizumab/bevacizumab arm and 14.6 months (95% CI, 11.2 months to not estimable) in the atezolizumab/placebo arm (stratified HR = 0.97, 95% CI = 0.64-1.47). The 6- and 12-month OS rates were 92% vs 80.5% and 59% vs 54.6%, respectively.
Grade 3 or 4 adverse events occurred in 74% of patients in each group. Serious adverse events were reported in 46% of the atezolizumab/bevacizumab group and 53% of the atezolizumab/placebo group. Treatment discontinuation due to adverse events occurred in 14% vs 11% of patients, respectively. Treatment-related deaths occurred in one patient (1.3%) in the combination arm and two patients (2.5%) in the placebo arm.
Expert Commentary
The study authors concluded that adding bevacizumab to atezolizumab plus cisplatin/gemcitabine improves PFS but not OS in unselected patients with advanced BTC. They also highlighted the potential of high VEGFA gene expression as a predictive biomarker, warranting further investigation. According to Anthony B. El-Khoueiry, MD, USC Norris Comprehensive Cancer Center, Los Angeles, the corresponding author for the Journal of Clinical Oncology article, further research is needed to validate these findings and explore the role of VEGFA as a biomarker in BTC treatment.
