“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, ASCO Expert in gastrointestinal cancers.

Results from the randomized international phase III TOPAZ-1 trial showed that the checkpoint immunotherapy durvalumab plus chemotherapy drugs gemcitabine and cisplatin significantly improved overall survival in patients with advanced biliary tract cancer compared to patients who received a placebo plus the chemotherapy drugs. Biliary tract cancer is classified as a rare disease comprised primarily of bile duct and gallbladder cancers.

The study will be presented at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, taking place January 20-22, 2022, in San Francisco, California.

Durvalumab is an immune checkpoint inhibitor that blocks the PD-L1 protein on the surface of immune cells, thereby allowing the immune system to recognise and attack tumour cells.

Gemcitabine promotes the death of cancer cells that are rapidly dividing. Cisplatin blocks DNA repair mechanisms in cancer cells, leading to their death.

“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 in the Division of Medical Oncology, Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, and principal investigator in the TOPAZ-1 phase III trial.

It is estimated there were 11,980 new cases of gallbladder cancer diagnosed in the United States (U.S.) in 2021, with an estimated 4,310 deaths1. Patients with biliary tract cancer are often diagnosed when the cancer is already at an advanced stage, which is one of the reasons why survival rates are so low.

Gemcitabine plus cisplatin has been the chemotherapy standard of care for most advanced biliary tract cancers in the U.S. In February 2018, the U.S. Food and Drug Administration approved durvalumab after chemoradiation for unresectable stage III non-small cell lung cancer.

In the study, patients who had not previously been treated for inoperable, locally advanced, recurrent, or metastatic biliary tract cancer were randomly assigned to receive durvalumab or a placebo. All patients also received the current chemotherapy standard of care for the disease, gemcitabine plus cisplatin.

Patients had one of three types of biliary tract cancer: 55% had intrahepatic cancers, which arise in the bile ducts inside the liver; 19 % had extrahepatic cancers, which form outside the liver; and 25% had gallbladder cancer.

The trial was conducted in the U.S. and 17 countries, including those in Europe and South America. Nearly 55% of the enrollees were from countries in Asia, including South Korea, Thailand, Japan, and China.

The risk of death for those taking durvalumab was 20% less than those who received the placebo. After a year and a half on the trial, 35.1% of patients who received durvalumab were still alive compared to 25.6% for placebo; at two years, it was 24.9% vs 10.4%, respectively.

Progression-free survival was significantly better with durvalumab compared to placebo, with a 25% lower risk of disease progression for those who received the immunotherapy. The overall response rate (meaning that the cancer regressed more than 30%) to durvalumab was 26.7% compared to 18.7% for the placebo. The most common side effects were anaemia (experienced by 48.2% of patients), neutropenia (31.7%) and nausea (40.2%).

Potentially serious side effects occurred in 62.7% of patients receiving durvalumab vs 64.9% for placebo, indicating that the majority of side effects in both arms are from chemotherapy.

“We are hopeful that durvalumab plus gemcitabine and cisplatin will become a new standard of care for advanced biliary tract cancer,” said Dr. Oh. “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.”

The researchers are hoping to develop more studies to explore a range of immunotherapy options for biliary tract cancer.

Source: ASCO