Bevacizumab-Erlotinib Switch Maintenance Improved Progression-Free Survival Among Patients With Advanced Biliary Tract Cancers

According to results from a phase 2/3 study, bevacizumab-erlotinib switch maintenance improved progression-free survival (PFS), with acceptable safety, compared to active surveillance among patients with chemotherapy-responsive advanced biliary tract cancers. 

“The concurrent addition of immune checkpoint inhibitors such as durvalumab or pembrolizumab to gemcitabine-cisplatin along with the continuation of the [immune checkpoint inhibitors] as maintenance therapy beyond 6 months in patients responding to treatment…is now considered the standard of care,” stated Anant Ramaswamy, MD, Tata Memorial Hospital, Mumbai, India, and coauthors. In this study, investigators sought to determine whether switch maintenance with bevacizumab and erlotinib, a regimen study authors described as “well-tolerated, efficacious, and cost-effective,” has a role in treating chemotherapy-responsive advanced biliary tract cancers.  

In this investigator-initiated open-label study, researchers enrolled 98 patients with histologically confirmed advanced biliary tract adenocarcinoma who experienced disease stabilization after 6 months of gemcitabine-based chemotherapy. Patients were randomized on a 1-to-1 basis to receive either active surveillance (n = 49) or 5 mg/kg of intravenous bevacizumab once every 21 days plus 100 mg of erlotinib once daily (n = 49) until disease progression, unacceptable toxicity, or patient withdraw. The primary end point was PFS. A key secondary end point was safety. 

At a median follow-up of 13.4 months, the 6-month PFS rate was 21.9% in the surveillance arm and 44.3% in the bevacizumab-erlotinib arm. Median PFS were 3.1 months and 5.3 months, respectively (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.33 to 0.74; P = .001). Grade 3 class-specific treatment-related adverse events with erlotinib included acneiform rash (2%) and oral stomatitis (2%). The most frequent grade 3 class-specific treatment-related adverse event with bevacizumab was bleeding. Six patients temporarily stopped erlotinib due to side effects and 2 patients temporarily stopped bevacizumab due to grade 2 proteinuria and hemorrhage esophageal varices. No treatment-related deaths were observed.

“The combination of bevacizumab-erlotinib as switch maintenance was well tolerated and achieved its primary end point of improving PFS compared with active surveillance in patients with [biliary tract cancers] who had previously received 6 months of gemcitabine-based chemotherapy,” concluded Dr Ramaswamy et al. “The study now moves on to the phase III component of the trial evaluating improvement in [overall survival] as the primary end point.”

“Maintenance therapy is gaining traction beyond colorectal cancer in several GI cancers,” added Journal of Clinical Oncology Associate Editor Eileen M. O’Reilly, MD, Memorial Sloan Kettering Cancer Center, New York. “This trial supports further development of non-cytotoxic maintenance therapy in advanced biliary cancers.” 

Source:

Ramaswamy A, Bhargava P, Srinivas S, et al. Bevacizumab erlotinib switch maintenance in chemo-responsive advanced gallbladder and cholangiocarcinoma (BEER BTC): A multicenter, open-label, randomized, phase II trial. J Clin Oncol. Published online: August 5, 2024. doi: 10.1200/JCO.23.02420