Durvalumab Plus Chemotherapy Reduces Risk of Death in Advanced Biliary Tract Cancer

Durvalumab plus chemotherapy did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.

Study results from the TOPAZ-1 clinical trial have found that treatment with durvalumab plus chemotherapy reduced the risk of death by 20% in first-line advanced biliary tract cancer.

The study investigators noted significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) versus chemotherapy alone as a first-line treatment. The results were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

Biliary tract cancer is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder. According to a press release from AstraZeneca, approximately 210,000 patients globally are diagnosed with biliary tract cancer each year and these patients have a poor prognosis, with approximately 5% to 15% of all patients surviving 5 years.

“After minimal progress for more than a decade in advanced biliary tract cancer, the TOPAZ-1 results are a tremendous advance for our patients, showing a clear survival benefit for IMFINZI added to chemotherapy compared to standard of care with a remarkable safety profile,” said Do-Youn Oh, MD, principal investigator in the TOPAZ-1 phase 3 trial, in the press release. “This is a potential new standard of care for patients in this setting and we remain committed to making advances in gastrointestinal cancers with high unmet need.”

The TOPAZ-1 trial is a randomized, double-blind, placebo-controlled, multicenter, global phase 3 trial of durvalumab in combination with chemotherapy as a first-line treatment in 685 patients with unresectable advanced or metastatic biliary tract cancer, including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. Researchers excluded patients with ampullary carcinoma.

A predefined interim analysis found that patients treated with durvalumab in combination with standard-of-care chemotherapy experienced a 20% reduction in the risk of death. The median OS was 12.8 months versus 11.5 for chemotherapy and an estimated 25% of patients were still alive at 2 years versus 10% for chemotherapy.

Study findings also showed a 25% reduction in the risk of disease progression or death with durvalumab plus chemotherapy. Median PFS was 7.2 months for the combination compared with 5.7 for chemotherapy alone. Furthermore, patients treated with durvalumab plus chemotherapy achieved an objective response rate (ORR) of 26.7% versus an ORR of 18.7% for patients in the chemotherapy alone arm.

Notably, durvalumab plus chemotherapy did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone. Grade 3 or 4 treatment-related AEs were experienced by 62.7% of patients treated with durvalumab compared with 64.9% of patients receiving chemotherapy alone.

“The results from the TOPAZ-1 trial challenge treatment expectations in advanced biliary tract cancer and provide compelling evidence that longer-term survival is possible,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in the press release. “Overall survival improves over time with an estimated 1 in 4 patients on Imfinzi plus chemotherapy alive at 2 years compared to 1 in 10 on chemotherapy alone. This is a potential new standard of care for patients in this setting and we remain committed to making advances in gastrointestinal cancers with high unmet need.”

REFERENCE

Imfinzi (durvalumab) plus chemotherapy reduced risk of death by 20% in 1st-line advanced biliary tract cancer. News release. AstraZeneca; January 18, 2022. Accessed March 1, 2022. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2022/imfinzi-durvalumab-plus-chemotherapy-reduced-risk-of-death-by-20-percent-in-1st-line-advanced-biliary-tract-cancer-01182022.html