Durvalumab Plus Chemo Continues to Improve Survival in Biliary Tract Cancer

Illustration of biliary tract cancer: ©freshidea - stock.adobe.com

Durvalumab (Imfinzi) plus standard-of-care chemotherapy led to a clinically meaningful benefit in overall survival (OS) at 3 years among patients with advanced biliary tract cancer, according to follow-up data from the phase 3 TOPAZ-1 trial (NCT03875235).¹

At a follow-up for 41.3 months, durvalumab plus chemotherapy reduced the risk of death by 26% vs chemotherapy alone (HR, 0.74; 95% CI, 0.63-0.87). In the combination arm, the median OS was 12.9 vs 11.3 months in the chemotherapy arm, and 14.6% of patients were alive at 3 years in the combination arm vs 6.9% in the chemotherapy arm.

These data will be presented at the 2024 Cholangiocarcinoma Foundation Conference on April 18, 2024.

"After 3 years of follow-up, durvalumab plus gemcitabine and cisplatin continued to demonstrate clinically meaningful long-term survival benefit with an acceptable safety profile, further supporting its use as a standard-of-care treatment in patients with locally advanced or metastatic biliary tract cancer," Aiwu Ruth He, MD, PhD, lead investigator in the TOPAZ-1 phase 3 trial, associate professor of medicine, leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, told Targeted Oncology^TM. "These results represent the longest survival follow-up ever reported for an immunotherapy treatment in this setting."

Regarding safety, durvalumab plus chemotherapy was well-tolerated, and no new safety signals were identified with the 3-year follow-up. Treatment-related serious adverse events (AEs) were reported in 15.4% of patients receiving durvalumab and chemotherapy vs 17.3% in those receiving chemotherapy alone.

"The results established the role of immunotherapy in combination with chemotherapy as a 1st line systemic treatment for advanced biliary tract cancer. The 14.6% survival rate at 3 years for advanced biliary tract cancer is progress made in treating this challenging cancer. We hope to improve patient outcomes further by incorporating novel immunotherapy combinations with systemic chemotherapy in future clinical trials," added He.

In October 2021, the TOPAZ-1 study met its primary end point of OS at a planned interim analysis. Durvalumab plus chemotherapy reduced the risk of death by 20% compared with chemotherapy alone (HR, 0.80; 95% CI, 0.66-0.97; 2-sided P =.021).

In TOPAZ-1, a total of 685 patients were randomized to receive durvalumab (n = 341) or placebo (n = 344) plus chemotherapy.² The objective response rate was 26.7% in the durvalumab arm vs 18.7% in the placebo arm (OR, 1.60; 95% CI, 1.11-2.31), and the median progression-free survival was 7.2 months (95% CI, 6.7-7.4) with durvalumab vs 5.7 months (95% CI, 5.6-6.7) with placebo. Seven patients (2.1%) achieved a complete response with durvalumab compared with 2 (0.6%) treated with placebo. Grade 3 and 4 AEs were reported in 75.7% and 77.8% of patients, respectively.

"Immunotherapy in combination of chemotherapy should be offered to patient with advanced biliary tract cancer if there is no absolute contraindication," said He.

REFERENCES:

1. Imfinzi plus chemotherapy doubled overall survival rate at three years for patients with advanced biliary tract cancer in TOPAZ-1 phase III trial. News release. AstraZeneca. April 16, 2024. Accessed April 16, 2024. https://tinyurl.com/3yy3mvph

2. Oh D, He A, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015. doi:10.1056/EVIDoa2200015