On September 2, 2022, durvalumab was approved for use in combination with gemcitabine/cisplatin for the treatment of patients with locally advanced or metastatic biliary tract cancer.1
Supporting Efficacy Data
Approval was based on findings in the double-blind TOPAZ-1 trial (NCT03875235), in which 685 patients with no previous systemic therapy for advanced disease were randomly assigned to durvalumab at 1,500 mg (n = 341) or placebo (n = 344) on day 1 plus gemcitabine at 1,000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of 21-day cycles for up to eight cycles, followed by durvalumab or placebo every 4 weeks. Median overall survival was 12.8 months (95% confidence interval [CI] = 11.1–14 months) in the durvalumab group vs 11.5 months (95% CI = 10.1–12.5 months) in the control group (hazard ratio [HR] = 0.80, 95% CI = 0.66–0.97, P = .021). Median progression-free survival was 7.2 months (95% CI = 6.7–7.4 months) vs 5.7 months (95% CI = 5.6–6.7 months; HR = 0.75, 95% CI = 0.63–0.89, P = .001). An objective response was observed in 27% vs 19% of patients.
How It Is Used
The recommended dose in patients weighing at least 30 kg is 1,500 mg every 3 weeks during combined treatment with gemcitabine/cisplatin, followed by 1,500 mg every 4 weeks as a single agent until disease progression or unacceptable toxicity. For patients weighing less than 30 kg, the recommended dose is 20 mg/kg every 3 weeks with gemcitabine and cisplatin followed by 20 mg/kg every 4 weeks until disease progression or unacceptable toxicity.
In TOPAZ-1, the most common adverse events of any grade in the durvalumab group were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia. The most common grade 3 or 4 laboratory abnormalities in the durvalumab group were hyponatremia, increased gamma-glutamyltransferase, and increased bilirubin. Serious adverse events occurred in 47% of the durvalumab group, and durvalumab was discontinued due to adverse events in 6% of patients. Fatal adverse events occurred in 3.6% of patients, including ischemic/hemorrhagic stroke, sepsis, and upper gastrointestinal hemorrhage.
Durvalumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, hepatitis, colitis, endocrinopathies, dermatologic reactions, nephritis and renal dysfunction, and solid organ transplant rejection; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity.
Durvalumab has warnings/precautions for immune--mediated adverse reactions, infusion-related reactions, complications of allogeneic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving durvalumab.
1. Imfinzi (durvalumab) injection prescribing information, AstraZeneca, September 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s035lbl.pdf. Accessed November 16, 2022.