Durvalumab Added to Gemcitabine and Cisplatin Improves Outcomes in Biliary Tract Cancer Across Primary Tumor Locations

The addition of durvalumab to gemcitabine and cisplatin in the first-line treatment setting is associated with improved efficacy outcomes among patients with advanced biliary tract cancer across all primary tumor locations (intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer), according to results from an exploratory subgroup analysis of the phase 3 TOPAZ-1 study.

Aiwu Ruth He, MD, Lombardi Comprehensive Cancer Center, Washington, DC, presented these results at the 2022 ESMO World Congress on Gastrointestinal Cancer.

The TOPAZ-1 study enrolled 810 patients with biliary tract cancer. Patients were randomized in a 1:1 ratio to receive gemcitabine and cisplatin on day 1 and 8 every 3 weeks, and either durvalumab or placebo on day 1 every 3 weeks for up to 8 cycles, followed by either durvalumab or placebo monotherapy until disease progression, unacceptable toxicity, or other discontinuation criteria were met.

This exploratory subgroup analysis aimed to examine efficacy outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), by primary tumor location.

Of the 810 patients enrolled on the trial, 383 had intrahepatic cholangiocarcinoma, 131 had extrahepatic cholangiocarcinoma, and 171 had gallbladder cancer.

For OS, the hazard ratios (HRs) favored the durvalumab cohort: 0.76 (95% confidence interval [CI], 0.58 to 0.98) for intrahepatic cholangiocarcinoma, 0.76 (95% CI, 0.49 to 1.19) for extrahepatic cholangiocarcinoma, and 0.94 (95% CI, 0.65 to 1.37) for gallbladder cancer. Researchers performed a regional analysis on patients with gallbladder cancer to understand the higher HR seen in these patients. In Asia, the HR for OS for gallbladder cancer was 0.82 (95% CI, 0.48 to 1.40) and in Europe plus North America the HR for OS was 0.78 (95% CI, 0.44 to 1.37).

The HRs for PFS in the durvalumab cohort were 0.79 (95% CI, 0.64 to 0.99) for intrahepatic cholangiocarcinoma, 0.52 (95% CI, 0.35 to 0.78) for extrahepatic cholangiocarcinoma, and 0.90 (95% CI, 0.65 to 1.24) for gallbladder cancer. Patients in the durvalumab cohort had better ORR vs placebo in all primary tumor locations: 24.7% vs 15.5% (odds ratio [OR], 1.79; 95% CI, 1.07 to 2.97) in intrahepatic cholangiocarcinoma, 28.8% vs 15.6% (OR, 2.18; 95% CI, 0.92 to 5.16) in extrahepatic cholangiocarcinoma, and 29.4% vs 27.9% (OR, 1.08; 95% CI, 0.55 to 2.09) in gallbladder cancer.

In addition, there was a higher percentage of responders with a DOR of at least 9 and 12 months in the durvalumab arm compared to the placebo arm for all tumor locations. The percentage of 9-month DOR in intrahepatic cholangiocarcinoma was 28.3% with durvalumab vs 24% with placebo, 43.3% vs 23.3% in extrahepatic cholangiocarcinoma, and 33.2% vs 27.5% in gallbladder cancer. The percentage of 12-month DOR with durvalumab vs placebo was 18.9% vs 12% in intrahepatic cholangiocarcinoma, 43.3% vs 23.3% in extrahepatic cholangiocarcinoma, and 27.6% vs 16.5% in gallbladder cancer.

As the benefit of durvalumab was consistent across all primary tumor locations, these findings support the addition of durvalumab to gemcitabine and cisplatin as a treatment option for patients with biliary tract cancer, regardless of the primary tumor location.

Source:

He A, Valle J, Ikeda M, et al. Outcomes by primary tumour location in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract LBA O-1.