First-Line Durvalumab/Chemotherapy Combo Results in Meaningful Survival Benefit in Advanced Biliary Tract Cancer

Patients with advanced biliary tract cancer received a clinically meaningful and statistically significant overall survival benefit after being treated with durvalumab and chemotherapy.

Treatment with durvalumab (Imfinzi) in combination with chemotherapy resulted in overall survival (OS) that was both statistically significant and clinically meaningful compared with chemotherapy alone in patients with advanced biliary tract cancer, according to a press release from developer AstraZeneca.

Positive high-level findings came from the phase 3 TOPAZ-1 trial (NCT03875235), wherein the study’s independent data monitoring committee indicated that the study met its primary end point of improved OS. Investigators also noted that the combination regimen resulted in an improvement in progression-free survival and overall response rate, both of which were secondary end points.

Data from the trial are set to be presented at an upcoming medical meeting.

“Patients with advanced biliary tract cancer are in dire need of new treatments as progress in the 1st-line setting has remained largely stagnant for more than 10 years. TOPAZ-1 is the first phase III trial to show that adding an immunotherapy to standard chemotherapy delivers a meaningful overall survival benefit for patients in this setting. Today’s exciting results are a major step forward in treating this disease and represent new hope for our patients,” Do-Youn Oh, MD, PhD, principal investigator and professor of the 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.

The global, double-blind, randomized, placebo-controlled multicenter trial attempted to assess the efficacy of durvalumab plus gemcitabine and cisplatin versus chemotherapy alone as a first-line therapy in patients with unresectable advanced or metastatic biliary tract cancer, including those with intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer (n = 685).

Patients in the experimental arm received durvalumab every 3 weeks via intravenous infusion, as well as gemcitabine and cisplatin for up to 8 cycles followed by single-agent durvalumab every 4 weeks until either disease progression or other discontinuation. The control group received the same chemotherapy backbone plus placebo.

Patients were required to have histologically confirmed disease to enroll on the trial. Those with unresectable, previously untreated biliary tract cancer or metastatic disease at initial diagnosis were also eligible for enrollment. Other inclusion criteria included recurrent disease over 6 months after curative surgery or completion of adjuvant therapy and a WHO/ECOG performance status of 0 or 1.

Those with a history of a different primary malignancy, brain metastases or spinal compression, or uncontrolled intercurrent disease were not eligible for enrollment. Other exclusion criteria included having a major surgical procedure within 28 days of first dose or prior locoregional therapy, including radioembolization.

“We are delighted TOPAZ-1 has been unblinded early due to clear evidence of efficacy for Imfinzi plus chemotherapy, which has also demonstrated a strong safety profile. We have now delivered two positive gastrointestinal cancer trials in a row for Imfinzi, following the HIMALAYA trial in liver cancer. We believe the significant survival benefit demonstrated marks a new era of immunotherapy treatment in this devastating disease and it advances our commitment to improving long-term survival for patients across these cancers where treatment options are limited,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, concluded.


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 October 26, 2021.