The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2022. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Combination durvalumab, gemcitabine, and cisplatin may be a new first-line standard of care for patients with advanced biliary tract cancer (BTC), according to researchers.

In the phase 3 TOPAZ-1 trial, adding durvalumab to gemcitabine and cisplatin improved both overall survival (OS) and progression-free survival (PFS).

These results were presented at the ASCO Gastrointestinal Cancers Symposium 2022 by Do-Youn Oh, MD, PhD, of Seoul National University Hospital in South Korea.

Continue Reading

Dr Oh noted that first-line standard care for advanced BTC has remained unchanged for over a decade, and TOPAZ-1 is the first phase 3 study to report positive results testing immunotherapy plus chemotherapy as first-line treatment for advanced BTC.

“Durvalumab plus gemcitabine-cisplatin is an effective first-line therapy and could become a new standard of care for patients with advanced biliary tract cancer,” Dr Oh said.

The TOPAZ-1 trial ( Identifier: NCT03875235) enrolled 685 patients who had locally advanced or metastatic BTC. The patients were randomly assigned to receive durvalumab (341 patients) or placebo (344 patients), each in combination with gemcitabine and cisplatin for up to 8 cycles. Patients then received durvalumab or placebo alone until disease progression or unacceptable toxicity.

Baseline characteristics were well balanced between the treatment arms. The median age was 64 years in both arms (overall range, 20-85 years), and more than half of patients were Asian. Roughly 56% of patients had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and nearly 20% had extrahepatic cholangiocarcinoma. About 80% of patients had unresectable disease at randomization.


The median follow-up was 16.8 months in the durvalumab arm and 15.9 months in the placebo arm. At the data cutoff, 18.6% of patients in the durvalumab arm and 5.8% in the placebo arm were still receiving study treatment; 42.5% and 49.4%, respectively, had received subsequent anticancer therapies.

The study’s primary endpoint was met, as durvalumab significantly improved OS. The median OS was 12.8 months with durvalumab and 11.5 months with placebo (hazard ratio [HR], 0.80; 95% CI, 0.66-0.97; P =.021). The 12-month OS rate was 54.1% and 48.0%, respectively, and the 24-month OS rate was 24.9% and 10.4%, respectively.

Durvalumab also improved PFS. The median PFS was 7.2 months with durvalumab and 5.7 months with placebo (HR, 0.75; 95% CI, 0.63-0.89; P =.001). The 6-month PFS rate was 58.3% and 47.2%, respectively, and the 12-month PFS rate was 16.0% and 6.6%, respectively.

The overall response rate was 26.7% in the durvalumab arm and 18.7% in the placebo arm (odds ratio, 1.60; 95% CI, 1.11-2.31; P =.011). The complete response rate was 1.2% and 0.6%, respectively.

There was no additional toxicity in the durvalumab arm compared with the placebo arm, Dr Oh noted.

The rate of grade 3/4 treatment-related adverse events (TRAEs) was 62.7% in the durvalumab arm and 64.9% in the placebo arm. The rate of TRAEs leading to treatment discontinuation was 8.9% and 11.4%, respectively. There were 2 fatal TRAEs in the durvalumab arm and 1 in the placebo arm.

The most common grade 3/4 TRAE was neutrophil count decrease, occurring in 20.7% of patients in the durvalumab arm and 25.4% of those in the placebo arm. The rate of grade 3 or higher immune-mediated events was 2.4% and 1.5%, respectively.

Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of ASCO GI 2022 by visiting the conference page.


Oh D-Y, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. Presented at ASCO GI 2022; January 20-22, 2022. Abstract 378.