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 (ClinicalTrials.gov identifier NCT03875235). In the trial, 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. Treatment continued until disease progression or unacceptable toxicity; treatment could continue beyond disease progression if patients were clinically stable and deriving clinical benefit, as determined by the investigators.

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. Dose reductions are not recommended.

Safety Profile

In TOPAZ-1, the most common adverse events of any grade in the durvalumab group were fatigue (42% vs 43% in the control group), nausea (40% vs 34%), constipation (32% vs 29%), decreased appetite (26% vs 23%), abdominal pain (24% vs 23%), rash (23% vs 14%), and pyrexia (20% vs 16%). The most common grade 3 or 4 adverse events included fatigue (6% vs 6%) and decreased appetite (2% vs 1%). The most common grade 3 or 4 laboratory abnormalities in the durvalumab group were hyponatremia (18%), increased gamma-glutamyltransferase (12%), and increased bilirubin (10%).

Serious adverse events occurred in 47% of the durvalumab group, most commonly cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Durvalumab was discontinued due to adverse events in 6% of patients, most commonly sepsis (three patients) and ischemic stroke (two patients). Fatal adverse events occurred in 3.6% of patients, including ischemic/hemorrhagic stroke (four patients), sepsis (two patients), and upper gastrointestinal hemorrhage (two patients).

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. Patients should be advised not to breastfeed while receiving durvalumab.

REFERENCE

1. Imfinzi (durvalumab) injection prescribing information, AstraZeneca, September 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s035lbl.pdf. Accessed November 16, 2022.