Adding Bevacizumab Improves PFS, But Not OS, in Advanced Biliary Tract Cancer
Bevacizumab in combination with atezolizumab and chemotherapy led to improvements in progression-free survival and duration of response in patients with advanced biliary tract cancer.
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The addition of bevacizumab (Avastin) to atezolizumab (Tecentriq) and cisplatin/gemcitabine (CisGem) led to improvements in progression-free survival (PFS) but not overall survival (OS) among patients with advanced biliary tract cancer (BTC), according to findings from the randomized, double-blind, phase 2 IMBrave151 study (NCT04677504).
The median PFS was 8.3 months with bevacizumab vs 7.9 months with placebo (stratified HR, 0.67; 95% CI, 0.46-0.95) among the 162 patients enrolled between February and September 2021. The median OS was 14.9 months with bevacizumab and 14.6 months with placebo (stratified HR, 0.97; 95% CI, 0.64-1.47). A high VEGFA was associated with a better PFS with bevacizumab vs placebo (HR, 0.44; 95% CI, 0.23-0.83).
In the bevacizumab arm, 92% (95% CI, 85.8-98.1) and 59% (95% CI, 47.7-70.3) of patients were alive at 6 and 12 months, respectively. In the placebo arm, 80.5% (95% CI, 72-89.1) of patients were alive at 6 months and 54.6% (95% CI, 43.7-65.4) were alive at 12 months.
“In the [intent-to-treat] population, the addition of bevacizumab to atezolizumab and CisGem was associated with a modest improvement in the primary end point of PFS. A PFS benefit of adding bevacizumab to chemoimmunotherapy was generally consistent across most of the prespecified subgroups and was sustained at 6 and 12 months. Although subgroup analyses should be interpreted with caution, patients with [intrahepatic cholangiocarcinoma] and [gallbladder cancer] appeared to derive greater PFS benefit from bevacizumab than those with [extrahepatic cholangiocarcinoma,” wrote authors of the study in findings published in the Journal of Clinical Oncology.
Patients were randomized 1:1 to receive 1200 mg of atezolizumab plus 15 mg/kg of bevacizumab or placebo once every 3 weeks until disease progression or unacceptable toxicity were observed. All patients also received 25 mg/m2 of cisplatin and 1000 mg/m2 of gemcitabine on days 1 and 8 every 3 weeks for up to 8 cycles.
For response, the investigator-assessed overall response rate (ORR) was 26.6% (95% CI, 17.3%-37.7%) with bevacizumab vs 26.5% (95% CI, 17.4%-37.3%) with placebo, and 1 complete response was observed in each arm. The median duration of response (DOR) was 10.3 months (95% CI, 6.7-16.7) in the bevacizumab arm vs 6.2 months (95% CI, 4.3-6.7) in the placebo arm (HR, 0.28; 0.12-0.68). In the bevacizumab arm, 47.8% (95% CI, 25.4%-70.3%) of patients had an ongoing response for 1 year vs 9.6% (95% CI, 0%-22.1%) in the placebo arm.
While the ORR was similar between arms, investigators proposed that the extended DOR in the bevacizumab arm “likely accounts for the trend in improved PFS for patients with complete or partial response.”
Regarding safety, grade 3 or 4 treatment-related adverse events (TRAEs) were reported in 69% of patients receiving bevacizumab vs 64% with placebo. Most events occurred in the induction phase and not in the maintenance phase in both arms, and the most common TRAEs were grade 1 or 2, including anemia, decreased neutrophil count, nausea, constipation, and decreased platelet count in both arms.
