Biliary tract cancer is a rare and often fatal disease comprised primarily of bile duct and gallbladder cancers; it is diagnosed in about 12,000 individuals each year in the United States. The cancer has a 5-year relative survival rate of 25% for localized intrahepatic bile duct cancers and just 15% for localized extrahepatic bile duct cancers.

Now, the results from the randomized international phase III TOPAZ-1 study investigating the PD-L1 inhibitor durvalumab in combination with the chemotherapy agents gemcitabine and cisplatin in patients with advanced biliary tract cancer showed the risk of death was 20% lower in patients receiving durvalumab and gemcitabine/cisplatin vs those receiving placebo plus gemcitabine/cisplatin. Progression-free survival was also significantly improved among patients treated with durvalumab vs placebo. The study’s findings indicate that durvalumab plus gemcitabine and cisplatin may be a new first-line standard of care regimen for the disease. The study by Oh et al is being presented at the 2022 ASCO Gastrointestinal Cancers Symposium (Abstract 378).

Study Methodology

In this double-blind study, patients previously untreated for unresectable locally advanced, recurrent, or metastatic biliary tract cancer were randomly assigned 1:1 to receive durvalumab or placebo plus gemcitabine and cisplatin for up to eight cycles followed by durvalumab or placebo until disease progression or unacceptable toxicity.

Random assignment was stratified by disease status, initially unresectable, recurrent, and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer). The primary endpoint was overall survival; the secondary endpoints included progression-free survival, objective response rate, and safety.

Results

As of the data cutoff for this interim analysis (August 2021), 685 patients were assigned to receive durvalumab plus gemcitabine/cisplatin (n = 341) or placebo plus gemcitabine/cisplatin (n = 344). The primary objective was met; durvalumab plus gemcitabine/cisplatin significantly improved overall survival vs placebo plus gemcitabine/cisplatin (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.66–0.97, P = .021). Progression-free survival was also significantly improved with durvalumab vs placebo (HR = 0.75, 95% CI = 0.64–0.89, P = .001). The objective response rate was 26.7% with durvalumab and 18.7% with placebo.

Grade 3 or 4 treatment-related adverse events occurred in 62.7% of the patients receiving durvalumab and in 64.9% of the patients receiving placebo. Treatment-related adverse events led to the discontinuation of any study medication in 8.9% of the patients receiving durvalumab and 11.4% of the patients receiving placebo.

Clinical Significance

“TOPAZ-1 is the first phase III trial to show that adding immunotherapy to standard chemotherapy can increase survival in biliary tract cancer and, importantly, does so without inducing any new serious side effects,” said 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, and principal investigator of this study, in a statement. “We are hopeful that durvalumab plus gemcitabine and cisplatin will become a new standard of care for advanced biliary tract cancer. Our first task at this time is boosting communication with patients and family members about the potential for this immunotherapy combination and what it may mean for their ongoing care.”

ASCO’s Perspective

Cathy Eng, MD, FACP, FASCO

“The current standard of care for inoperable biliary tract cancer is combined chemotherapy. That standard has not changed in over a decade. TOPAZ-1 is the first phase III trial to demonstrate the benefit of immunotherapy for improved overall survival, in combination with chemotherapy, creating a new standard of care. Patients have a greater reason for hope given the positive results seen with the use of immunotherapy in biliary tract cancers,” said Cathy Eng, MD, FACP, FASCO, ASCO Expert in gastrointestinal cancers, in a statement.

Disclosure: Funding for this study was provided by AstraZeneca. For full disclosures of the study authors, visit coi.asco.org.