Adding Durvalumab Immunotherapy to Chemotherapy Improves Survival in Biliary Tract Cancer

Biliary tract cancer is a rare and often aggressive disease arising from the bile ducts and gallbladder. About 12 thousand people are diagnosed each year in the USA, while the figure for Turkey is estimated at around 2 thousand. Apart from gallbladder cancer, biliary tract cancers are divided into intrahepatic (inside the liver) and extrahepatic (outside the liver) bile duct cancers. The 5-year relative survival rate is 25% for early-stage intrahepatic bile duct cancer and only 15% for early-stage extrahepatic bile duct cancer. Biliary tract cancers are also called cholangiocancer.

As a notable oncology development in early 2022, for patients with advanced biliary tract cancer, the PD-L1 inhibitor type of immunotherapy known as durvalumab was investigated in combination with the gemcitabine and cisplatin doublet chemotherapy regimen in the randomized international phase III TOPAZ-1 study. The results showed that patients receiving durvalumab had a 20% lower risk of death.

Compared with patients receiving cisplatin + gemcitabine + placebo, those given cisplatin + gemcitabine + durvalumab also had significantly better progression-free survival. The findings suggest that durvalumab plus gemcitabine and cisplatin could be a new first-line standard of care for the disease. The study by Dr. Do-Youn Oh and colleagues was presented at the 2022 ASCO Gastrointestinal Cancers Symposium.

TOPAZ-1 Study Details

In this double-blind study, previously untreated patients with locally advanced unresectable, recurrent, or metastatic biliary tract cancer were randomly assigned in a 1:1 ratio to the durvalumab or placebo arm, followed by durvalumab or placebo until disease progression or unacceptable side effects.

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

Results

As of the data cutoff for this interim analysis (August 2021), 341 of the 685 patients had been assigned to durvalumab plus gemcitabine/cisplatin and 344 to placebo plus gemcitabine/cisplatin.

• The primary endpoint was met: durvalumab plus gemcitabine/cisplatin significantly improved overall survival compared with placebo plus gemcitabine/cisplatin (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.66–0.97, P = 0.021). A 20% reduction in the risk of death.
• Progression-free survival was also significantly improved with durvalumab versus placebo (HR = 0.75, 95% CI = 0.64-0.89, P = 0.001). A 25% reduction in the risk of cancer progression.
• The objective response rate was 26.7% with durvalumab and 18.7% with placebo.
• Treatment-related grade 3 or 4 adverse events occurred in 62.7% of patients receiving durvalumab and 64.9% of those receiving placebo. Treatment-related adverse events led to discontinuation of any study drug in 8.9% of patients receiving durvalumab and 11.4% of those receiving placebo.

The Study’s Importance for Clinical Practice

The current standard of care for unresectable biliary tract cancer is combination chemotherapy. This standard has not changed for more than a decade. TOPAZ-1 is the first phase III clinical trial to show that adding immunotherapy to standard chemotherapy can improve survival in biliary tract cancer and, more importantly, do so without causing any new serious side effects. It has raised hopes for the use of immunotherapy in biliary tract cancers.

Durvalumab plus gemcitabine and cisplatin appears likely to become the new standard of care for advanced biliary tract cancer and receive FDA (US Food and Drug Administration) approval.