A multi-center, single-arm, retrospective study published in Therapeutic Advances in Gastroenterology investigated the efficacy and safety of combining atezolizumab, bevacizumab, and GEMOX (gemcitabine plus oxaliplatin) in patients with advanced biliary tract cancer (BTC). The study, conducted across three medical centers, suggests that this triple combination therapy may offer a promising treatment option for this aggressive malignancy.
Study Design and Patient Population
The study enrolled 30 patients with pathologically confirmed advanced BTC between March 2020 and September 2021. All patients received atezolizumab, bevacizumab, and GEMOX. Treatment response was evaluated using both mRECIST and RECIST v1.1 criteria. The primary endpoint was the overall response rate (ORR), while secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety.
Significant Efficacy Observed
The results showed a best ORR of 76.7%, with 20% of patients achieving a complete response (CR) and 56.7% achieving a partial response (PR). The disease control rate (DCR) was 90.0%. The median PFS was 12.0 months (95% CI, 6.1–17.9), and the median OS was not reached during the follow-up period. These outcomes compare favorably with historical data for GEMOX alone or GEMOX combined with other targeted agents.
Safety Profile and Adverse Events
The treatment-related adverse events (TRAEs) were manageable. The most common TRAEs included fever (73.3%), neutropenia (63.3%), and increased aspartate transaminase (AST) and alanine aminotransferase (ALT) levels (50.0% and 43.3%, respectively). Grade ≥3 TRAEs occurred in 10.0% of patients, with neutropenia being the most frequent. Two patients discontinued treatment due to TRAEs, and no treatment-related deaths were reported.
Biomarker Analysis
Exploratory biomarker analysis using whole exome sequencing of pathological tissues from nine patients suggested that alterations in the ALS2CL gene may be associated with a higher ORR. Specifically, patients with altered ALS2CL had an ORR of 100.0% compared to 0% in those with the wild-type gene (p < 0.01).
Clinical Implications
These findings suggest that the combination of atezolizumab, bevacizumab, and GEMOX may be an effective and safe treatment option for patients with advanced BTC. The study highlights the potential for anti-PD-L1/VEGF inhibition combined with chemotherapy to enhance antitumor immunity and improve clinical outcomes. Further prospective studies with larger cohorts are warranted to validate these results and to further investigate the role of ALS2CL as a predictive biomarker.
