FDA Grants Priority Review to Durvalumab Plus Chemo in Locally Advanced or Metastatic Biliary Tract Cancer

The results of the phase 3 TOPAZ-1 trial led to the priority review of durvalumab plus chemotherapy in patients with locally advanced biliary tract cancer.

The FDA has granted priority review to durvalumab (Imfinzi) plus standard of care chemotherapy for patients with locally advanced or metastatic biliary tract cancer, according to a press release from AstraZeneca.1

The priority review is based on results of the phase 3 TOPAZ-1 trial (NCT03875235) which highlighted a median overall survival of 12.8 months (95% CI, 11.1-14.0) for the combination group compared with 11.5 months (95% CI, 10.1-12.5) in the chemotherapy group.2 Investigators also reported a 20% reduction in risk of death compared with chemotherapy alone (HR, 0.80; 95% CI, 0.66-0.97; 2-sided P = .021). Investigators estimated that 1 in 4 patients who received the combination was alive at 2 years compared with 1 in 10 patients who received chemotherapy alone.

“People with advanced biliary tract cancer have faced poor outcomes and limited treatment options for too long, and today’s news for the TOPAZ-1 trial underscores the urgency to deliver new, effective therapies in this setting. We are working closely with the FDA to bring the first immunotherapy-based option to patients with this devastating cancer and potentially set a new standard of care with [durvalumab] plus chemotherapy,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in the press release.

The results of the trial were previously presented at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium. TOPAZ-1 was a randomized, double-blind, placebo-controlled trial of durvalumab plus gemcitabine and cisplatin vs chemotherapy alone as first-line treatment. The patients treated included those with unresectable advanced or metastatic biliary tract cancer which included intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer.3

The primary end point was OS, and the secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. A total of 685 patients enrolled on the study, 341 of whom were randomized to the durvalumab plus chemotherapy group and 344 were placed in the placebo plus chemotherapy group.

Patients had a median PFS of 7.2 months (95% CI, 6.7-7.4) in the combination group and 5.7 months (95% CI, 5.6-6.7) in the chemotherapy group (HR, 0.75; 95% CI, 0.64-0.89; P = .001). The ORR was 26.7% vs 18.7% in the combination and chemotherapy groups, respectively.

The median follow-up at data cut-off for OS was 13.7 months vs 12.6 months in the combination and chemotherapy groups, respectively.

“After minimal progress for more than a decade in advanced biliary tract cancer, the TOPAZ-1 results are a tremendous advance for our patients, showing a clear survival benefit for [durvalumab] added to chemotherapy compared with standard of care with a remarkable safety profile. This combination will provide a desperately needed and potentially practice-changing new treatment option in a setting where the current prognosis is devastating,” principal investigator Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology and Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, concluded.


  1. Imfinzi plus chemotherapy granted priority review in the US for patients with locally advanced or metastatic biliary tract cancer based on TOPAZ-1 phase III trial. News Release. AstraZeneca. May 4, 2022. Accessed May 4, 2022. https://bit.ly/3w3Yj9N
  2. Oh DY, 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. J Clin Oncol. 2022; 40(suppl 4):378-378. doi:10.1200/JCO.2022.40.4_suppl.378