The results were the longest survival follow-up ever reported for a phase 3 trial for biliary tract cancer.
Updated results from the TOPAZ-1 phase 3 trial showed that durvalumab (Imfinzi; AstraZeneca) combined with the standard-of-care chemotherapy demonstrated clinically meaningful long-term overall survival (OS) at 3 years for individuals with advanced biliary tract cancer, according to a press release from the company. The results were presented on April 18 at the 2024 Cholangiocarcinoma Foundation Conference in Salt Lake City, Utah, and were the longest survival follow-up ever reported for a phase 3 trial in this setting.1
“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. These results reinforce the long-term benefit of this immunotherapy-based combination as a standard of care for patients with this devastating disease,” Do-Youn Oh, MD, PhD, professor of the division of medical oncology in the Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, said in the press release.1
According to the American Cancer Society, cholangiocarcinoma, known as bile duct cancer, is diagnosed in approximately 8000 individuals in the United States each year. The average age of diagnosis for intrahepatic bile ducts is 70 years and extrahepatic bile ducts is 72 years.2
TOPAZ-1 is a randomized, double-blind, placebo-controlled, global phase 3 trial of durvalumab in combination with gemcitabine plus cisplatin as a first line treatment in 685 adults with unresectable, locally advanced or metastatic biliary tract cancer, including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. The primary end point included OS, with key secondary end points including progression-free survival, objective response rate, and safety. The trial was conducted across 17 countries, including the United States, Europe, South America, South Korea, Thailand, Japan, and China.1
The results showed that durvalumab with chemotherapy reduced the risk of death by 26% compared with chemotherapy alone, with an OS of 12.9 months vs 11.3 months, respectively. Furthermore, at 3 years, approximately 14.6% of patients on durvalumab plus chemotherapy compared with 6.9% of patients on chemotherapy alone were alive at the analysis. In October 2021, the primary end point of OS was met at the interim analysis, demonstrating that the combination reduced the risk of death by 20%.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. 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,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in a press release.1
Durvalumab plus chemotherapy was well tolerated, with no new safety signals observed in the longer follow up, with 15.4% of patients experiencing treatment-related serious adverse events with the combination and 17.3% with chemotherapy alone. For patients with locally advanced or metastatic biliary tract cancer, the most common adverse reactions included fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia. Discontinuation due to adverse reactions occurred in 6% of individuals receiving durvalumab plus chemotherapy, including cholangitis, pyrexia, anemia, sepsis, and acute kidney injury. Additionally, 3.6% experienced fatal adverse reactions.1
Currently, durvalumab in combination with gemcitabine and cisplatin is indicated for treatment of adults with locally advanced or metastatic biliary tract cancer, according to the press release.1
