FDA Grants Approval to Durvalumab Plus Chemotherapy for Locally Advanced or Metastatic Biliary Tract Cancer

The FDA has approved durvalumab for the treatment of patients with locally advanced or metastatic biliary tract cancer.

The FDA has approved durvalumab (Imfinzi) for the treatment of patients with locally advanced or metastatic biliary tract cancer.1

The approval was based on the results of the ongoing randomized, double-blind placebo controlled, multi-regional, international, TOPAZ-1 (NCT03875235) study that reached its primary end point of median overall survival and showed promise in its secondary end points of progression free-survival (PFS) and objective response rate (ORR).

In the 685-patient study, results showed that at a median follow up of 16.8 months(95% CI, 14.8-17.7) the median OS for patients treated with durvalumab was 12.8 months (95% CI, 11.1-14.0) compared with 11.5 months (95% CI, 10.1-12.5) in the placebo group at a median follow up of 15.9 months (95% CI, 14.9-16.9). Researchers observed a hazard ratio (HR) of 0.70 for the decrease in risk of death when durvalumab was added to treartment.2 Moreover, durvalumab in combination with chemotherapy reduced the risk of death in patients by 20% compared with chemotherapy alone (HR, 0.80; 95% CI, 0.66 - 0.97; P = 0.021). 

In the combination arm, the estimated 12-month OS was 54.1% (95% CI, 48.4-59.4) vs 48% (95% CI, 42.4-53.4) for patients on placebo/chemotherapy. At 18 months, the estimated OS rate was 35.1% (95% CI, 29.1-41.2) vs 25.6% (95% CI, 19.9-31.7), and at 24-months the OS rate was 24.9% (95% CI, 17.9-32.5) vs 10.4% (95% CI, 4.7-18.8), respectively. 


Median PFS observed in the durvalumab arm was 7.2 months (95% CI, 6.7-7.4) vs 5.7 months (95% CI, 5.6-6.7) in the placebo arm, with a HR of 0.75 (95% CI, 0.63-0.89; P =.001). The ORR in the treatment arm was 36.7% vs 18.7% in the placebo arm (Odds ratio, 1.60; 95% CI, 1.11-2.31). When added to chemotherapy durvalumab led to a 2.1% complete response rate compared with 0.6% in the placebo arm, and a partial response of 24.6% vs 18.1%, respectively. Overall, 32.6% of patients in the combination arm had a continued response at the time of data cutoff vs 25.3% and response continued for 12 months in 26.1% of patients on durvalumab vs 15% on placebo.

“People with advanced biliary tract cancer have faced poor outcomes and limited treatment options for too long, and today’s news for the TOPAZ-1 trial underscores the urgency to deliver new, effective therapies in this setting,” saidSusan Galbraith, executive vice president, oncology R&D of AstraZeneca, in a press release when the FDA accepted the biologics license application for durvalumab in this patient population.

Ultimately, 680 patients were evaluated for safety with the most common adverse events (AEs) being anemia (48.2%), nausea (40.2%), constipation (32.0%), and neutropenia (31.7%), for patients treated with durvalumab. The most common AEs for patients in the placebo group also included anemia (44.7%) and nausea, but a decreased neutrophil count (31%) as well.

Immune-mediated AEs were seen more in the durvalumab arm at 12.7% vs 4.7% in the placebo group, with grade 3 or 4 immune-mediated AEs were at 2.4% vs 1.5%, respectively. Treatment discontinuations were higher in the placebo group at 15.2% vs 13% in the durvalumab arm, and treatment-related deaths were higher in the placebo arm at 4.1% vs 3.6%, respectively.


1. FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. News release. September 2, 2022. Accessed September 2, 2022. https://bit.ly/3Qd2Kq

2. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evidence. Published online June 1, 2022. doi: 10.1056/EVIDoa2200015

3. First phase III trial in this setting to show improved overall survival with an immunotherapy added to chemotherapy over standard-of-care chemotherapy alone. AstraZeneca. News Release. May 4, 2022. Accessed May 4, 2022. https://bit.ly/3kFJfdi

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