Updated Phase III Trial Data Show Significant Survival Benefit for Imfinzi with Chemotherapy for Advanced Biliary Tract Cancer

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Results from the Phase III TOPAZ-1 trial (NCT03875235) found that Imfinzi (durvalumab; AstraZeneca) combined with standard-of-care chemotherapy consisting of gemcitabine plus cisplatin produced a clinically meaningful long-term overall survival (OS) benefit after three years in patients with advanced biliary tract cancer (BTC).¹ In September 2022, the Imfinzi plus chemotherapy became the first immunotherapy regimen approved by the FDA for patients with locally advanced or metastatic BTC.²

“The latest data from TOPAZ-1 show that twice as many patients with advanced [BTC] were still alive at three years with durvalumab and chemotherapy, an especially meaningful advance in a setting where historically the prognosis has been poor,” TOPAZ-1 principal investigator Do-Youn Oh, MD, PhD, professor, Division of Medical Oncology, Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, said in a press release. “These results reinforce the long-term benefit of this immunotherapy-based combination as a standard of care for patients with this devastating disease.”¹

BTC is a group of rare and aggressive gastrointestinal cancers that manifest in the bile ducts and the gallbladder. According to a press release, approximately 50,000 people in the United States, Europe, and Japan and approximately 210,000 people worldwide are diagnosed with BTC each year, with approximately 5% to 15% surviving for five years. Further, patients with metastatic BTC have a five-year survival rate of less than 5%.¹

Imfinzi is a human monoclonal antibody that attaches to the PD-L1 protein and prevents its interaction with the PD-1 and CD80 proteins, which inhibits the immune-evading ability of the tumor.²

The randomized, double-blind, placebo-controlled, multicenter, global TOPAZ-1 trial enrolled 685 adults with unresectable, locally advanced or metastatic BTC—including intrahepatic and extrahepatic cholangiocarcinoma—and gallbladder cancer. Investigators compared Imfinzi with gemcitabine plus cisplatin vs. placebo with chemotherapy in the first-line treatment setting. The trial’s primary endpoint was OS, with key secondary endpoints that included progression-free survival, objective response rate, and safety.

The trial results show that at more than three years with a median follow-up of 41.3 months, the Imfinzi with chemotherapy combination lowered the risk of death by 26% compared with chemotherapy alone. Median OS was 12.9 months in patients administered Imfinzi plus chemotherapy compared with 11.3 months in patients who received chemotherapy alone.

Further, 14.6% of patients in the Imfinzi with chemotherapy cohort were alive at three years compared with 6.9% of patients administered chemotherapy alone. Data released in October 2021 showed that at a planned interim analysis, Imfinzi plus chemotherapy achieved the primary endpoint of OS in lowering the risk of death by 20% compared with chemotherapy alone.³

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

In terms of safety, there were no new safety signals identified with longer follow-up in patients administered Imfinzi plus chemotherapy. Investigators found that 15.4% of patients in the Imfinzi plus chemotherapy cohort experienced treatment-related serious adverse events compared with 17.3% of patients administered chemotherapy alone.

“AstraZeneca’s longer survival data in advanced [BTC] represents a meaningful milestone in that we are seeing three-year survival data for the first time for these patients,” said Stacie Lindsey, CEO, Cholangiocarcinoma Foundation, in a press release. “The data spurs hope that research will continue to improve outcomes for patients living with these challenging and rare cancers.”¹

References

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 15, 2024. Accessed April 15, 2024. https://www.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. 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 April 15, 2024. https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-approved-in-us-for-biliary-tract-cancer.html

3. Imfinzi plus chemotherapy significantly improved overall survival in 1st-line advanced biliary tract cancer in TOPAZ-1 Phase III trial at interim analysis. News release. AstraZeneca October 25, 2021. Accessed April 15, 2024. https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improved-survival-in-biliary-tract-cancer.html#