Durvalumab Plus Chemotherapy Approved as First Immunotherapy Regimen for Treatment of Advanced Biliary Tract Cancer


Results from the TOPAZ-1 phase 3 trial showed that the combination reduced risk of death by 20% versus chemotherapy alone.

Officials with the FDA have approved durvalumab (Imfinzi; AstraZeneca) plus chemotherapy as the first immunotherapy regimen available for patients with locally advanced or metastatic biliary tract cancer (BTC).

BTC are a group of rare and aggressive cancers that occur in the bile ducts and the gallbladder. According to a press release, approximately 23,000 patients in the United States are diagnosed with BTC each year and these patients have a poor prognosis, with approximately 5% to 15% surviving 5 years.

Durvalumab is a human monoclonal antibody that binds to the programmed death-ligand 1 (PD-L1) protein and blocks the interaction of PD-L1 with the programmed cell death-1 (PD-1) and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses. It is also the only approved immunotherapy in the curative-intent setting of unresectable, stage 3 non-small cell lung cancer among patients whose disease has not progressed after chemoradiotherapy and is the global standard of care in this setting, according to the press release.

The approval in BTC is based on results from the TOPAZ-1 phase 3 trial, which showed that the combination reduced risk of death by 20% versus chemotherapy alone in an interim analysis. An estimated 1 in 4 patients treated with the combination were still alive at 2 years compared to 1 in 10 treated with chemotherapy alone, and results were consistent across all prespecified subgroups regardless of PD-L1 expression or tumor location.

“This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated, and effective treatment options after more than a decade of limited innovation,” said Aiwu Ruth He, MD, PhD, a lead investigator in the TOPAZ-1 phase 3 trial, in the press release. “The combination of durvalumab and chemotherapy should become a new standard of care in this setting, having demonstrated improved survival for these patients who have historically faced a poor prognosis.”

The TOPAZ-1 trial is a randomized, double-blind, placebo controlled, multicenter, global phase 3 trial of durvalumab in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy. It was administered as a first-line agent in 685 patients with unresectable advanced or metastatic BTC, including intrahepatic and extrahepatic cholangiocarcinoma, as well as gallbladder cancer. Patients with ampullary carcinoma were excluded.

The results were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium and published in the New England Journal of Medicine Evidence. The combination was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone, according to the press release.

In July 2022, the combination was added to the NCCN Clinical Practice Guidelines in Oncology as a Category 1 preferred regimen for first-line therapy in patients with locally advanced or metastatic BTC based on data from the TOPAZ-1 trial.

“For the first time, patients in the US with advanced biliary tract cancer have an immunotherapy-based option that meaningfully extends survival and is well-tolerated,” said Dave Frederickson, executive vice president of the Oncology Business Unit at AstraZeneca, in the press release. “This approval for Imfinzi and chemotherapy advanced our ambition to challenge treatment expectations and transform care for patients with gastrointestinal cancers with high unmet need.”


Imfinzi plus chemotherapy approved in the US as the first immunotherapy regimen for patients with advanced biliary tract cancer. News release. AstraZeneca; September 5, 2022. Accessed September 6, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-approved-in-us-for-biliary-tract-cancer.html

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