The Food and Drug Administration (FDA) has approved Imfinzi® (durvalumab), in combination with gemcitabine and cisplatin, for the treatment of adults with locally advanced or metastatic biliary tract cancer.
Imfinzi is a programmed death-ligand 1 (PD-L1) blocking antibody. The approval was based on data from the phase 3 TOPAZ-1 trial (ClinicalTrials.gov Identifier: NCT03875235), a double-blind, placebo-controlled study that included 685 patients with histologically confirmed locally advanced unresectable or metastatic biliary tract cancer who had not previously received systemic therapy.
Patients were randomly assigned to receive durvalumab plus gemcitabine and cisplatin (n=341) or placebo plus gemcitabine and cisplatin (N=344); treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); investigator-assessed progression free survival (PFS), objective response rate (ORR) and duration of response were designated as additional efficacy outcome measures.
Results showed a statistically significant improvement in OS with durvalumab plus chemotherapy compared with placebo plus chemotherapy (12.8 months [95% CI, 11.1-14] vs 11.5 months [95% CI, 10.1-12.5]; hazard ratio [HR], 0.80 [95% CI, 0.66-0.97]; P =.021).
Median PFS was reported to be 7.2 months (95% CI, 6.7-7.4) in the durvalumab arm and 5.7 months (95% CI, 5.6-6.7) in the placebo arm (HR, 0.75 [95% CI, 0.63-0.89]). The investigator-assessed ORR was 27% (95% CI, 22-32) and 19% (95% CI, 15-23) in the durvalumab and placebo arms, respectively.
Fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia were reported to be the most common adverse reactions with treatment.
“This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated and effective treatment options after more than a decade of limited innovation,” said Aiwu Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, and a lead investigator in the TOPAZ-1 phase 3 trial. “The combination of durvalumab and chemotherapy should become a new standard of care in this setting, having demonstrated significantly improved survival for these patients who have historically faced a poor prognosis.”
- Imfinizi® (durvalumab) plus chemotherapy approved in the US as the first immunotherapy regimen for patients with advanced biliary tract cancer. News release. September 5, 2022. https://www.businesswire.com/news/home/20220905005055/en/IMFINZI%C2%AE-durvalumab-Plus-Chemotherapy-Approved-in-the-US-as-the-First-Immunotherapy-Regimen-for-Patients-with-Advanced-Biliary-Tract-Cancer
- Imfinzi. Package insert. AstraZeneca; 2022. Accessed September 6, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s035lbl.pdf