Durvalumab Plus Chemo Sustains 3-Year OS Benefit in Advanced Biliary Tract Cancer


Durvalumab plus chemotherapy produced superior 3-year survival outcomes vs chemotherapy alone in advanced biliary tract cancer.

Do-Youn Oh, MD, PhD

Do-Youn Oh, MD, PhD

Updated findings from an exploratory analysis of the phase 3 TOPAZ-1 trial (NCT03875235) demonstrated that durvalumab (Imfinzi) plus standard-of-care (SOC) chemotherapy maintained a clinically meaningful improvement in overall survival (OS) at 3 years compared with chemotherapy alone in patients with advanced biliary tract cancer.1

At a median follow-up of 41.3 months, durvalumab plus chemotherapy reduced the risk of death by 26% vs chemotherapy alone (HR, 0.74; 95% CI, 0.63-0.87). Patients treated with the combination (n = 341) achieved a median OS of 12.9 months (95% CI, 11.6-14.1) compared with 11.3 months (95% CI, 10.1-12.5) for those who received chemotherapy plus placebo (n = 344). Moreover, the 3-year OS rate was 14.6% (95% CI, 11.0%-18.6%) in the combination arm vs 6.9% (95% CI, 4.5%-10.0%) in the placebo arm.

Regarding safety, the combination regimen continued to be tolerable, and no new safety signals were observed. Treatment-related serious adverse effects with the combination occurred in 15.4% of patients; these occurred in 17.3% of patients treated with chemotherapy plus placebo.

This readout marks the longest survival follow-up reported for a global, randomized, phase 3 immunotherapy trial for patients with advanced biliary tract cancer. Detailed findings from this exploratory analysis will be presented on April 18 at the 2024 Cholangiocarcinoma Foundation Conference in Salt Lake City, Utah.

“The latest data from TOPAZ-1 show that twice as many patients with advanced biliary tract cancer were still alive at 3 years with durvalumab and chemotherapy, an especially meaningful advance in a setting where historically the prognosis has been poor,” principal investigator Do-Youn Oh, MD, PhD, stated in a news release. “These results reinforce the long-term benefit of this immunotherapy-based combination as a SOC for patients with this devastating disease.” Oh is also a professor in the Division of Medical Oncology, the Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine in South Korea.

On September 2, 2022, the FDA approved durvalumab plus gemcitabine and cisplatin for the treatment of adult patients with locally advanced or metastatic biliary tract cancers, based on previously reported findings from TOPAZ-1.2 In a prespecified interim analysis, the study met its primary OS end point with durvalumab plus chemotherapy, which produced a median OS of 12.8 months (95% CI, 11.1-14.0) vs 11.5 months (95% CI, 10.1-12.5) with chemotherapy alone (HR, 0.80; 95% CI, 0.66-0.97; P =.021).

TOPAZ-1 was a randomized, double-blind, placebo-controlled, multicenter trial that enrolled 685 patients with histologically confirmed, locally advanced, unresectable or metastatic biliary tract cancer who had not previously received systemic therapy for advanced disease.1,3 Eligible patients were at least 18 years of age with an ECOG performance status of 0 or 1, and 1 or more measurable lesions per RECIST v1.1 criteria. Exclusion criteria included ampullary carcinoma; active or previous documented autoimmune or inflammatory disorders; prior exposure to immune-mediated therapy; or a known allergy or hypersensitivity to any study treatment.

The trial was conducted at 105 centers across 17 countries including in the United States, Europe, South America, and Asia.1 Patients were randomly assigned 1:1 to receive 1500 mg of durvalumab (n = 341) or placebo (n = 344) on day 1 of each 21-day cycle in combination with gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of each cycle for up to 8 cycles.3 This was followed by durvalumab or placebo monotherapy every 4 weeks until disease progression or unacceptable toxicity. Stratification was based on disease status (initially resectable vs recurrent) and primary tumor location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer).3

The primary end point of the trial was OS, and secondary end points included progression-free survival, objective response rate, and safety.1

“TOPAZ-1 raised the bar for the treatment of advanced biliary tract cancer, showing a remarkable survival benefit for [durvalumab] added to chemotherapy with a well-tolerated regimen,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, added in the press release. “These data represent the longest survival follow-up reported for immunotherapy in this setting, and the 3-year landmark survival improvement underscores our commitment to improving long-term outcomes in gastrointestinal cancers.”


  1. Imfinzi plus chemotherapy doubled overall survival rate at three years for patients with advanced biliary tract cancer in TOPAZ-1 phase III trial. News release. AstraZeneca. April 16, 2024. Accessed April 16, 2024. https://od-prod-origin-astrazeneca-corporate.digital-astrazeneca.com/media-centre/press-releases/2024/imfinzi-plus-chemotherapy-doubled-overall-survival-rate-at-three-years-for-patients-with-advanced-biliary-tract-cancer-in-topaz-1-phase-iii-trial.html
  2. FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. FDA. September 2, 2022. Accessed April 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer
  3. Oh D, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015. doi:10.1056/EVIDoa2200015
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