FDA Approves Durvalumab in Combination Regimen for Advanced or Metastatic Biliary Tract Cancer

By: JNCCN 360 Staff
Posted: Friday, September 30, 2022

On September 2, the U.S. Food and Drug Administration (FDA) approved the PD-L1 inhibitor durvalumab (Imfinzi) in combination with gemcitabine and cisplatin for adults with locally advanced or metastatic biliary tract cancer. Efficacy was evaluated in the phase III TOPAZ-1 trial (ClinicalTrials.gov identifier NCT03875235). This randomized, double-blind, placebo-controlled, multiregional study enrolled 685 patients with histologically confirmed locally advanced unresectable or metastatic biliary tract cancer who had not previously received systemic therapy for advanced disease.

In TOPAZ-1, 56% of patients had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma. Patients were randomly assigned 1:1 to receive one of two regimens: durvalumab plus gemcitabine and cisplatin, followed by durvalumab, or placebo plus gemcitabine and cisplatin, followed by placebo.

The major efficacy outcome measure was overall survival. A statistically significant improvement in overall survival was demonstrated with durvalumab vs placebo. Median overall survival was 12.8 months (95% confidence interval [CI] = 11.1–14) months and 11.5 months (95% CI = 10.1–12.5 months) with durvalumab and placebo, respectively (hazard ratio = 0.80; 95% CI = 0.66–0.97, P = .021). The median progression-free survival was 7.2 months (95% CI = 6.7–7.4 months) and 5.7 months (95% CI = 5.6–6.7 months) with durvalumab and placebo, respectively. Investigator-assessed overall response rate was 27% (95% CI = 22%–32%) and 19% (95% CI = 15%–23%) in the durvalumab and placebo arms, respectively.

The most common (≥ 20%) adverse reactions occurring in patients were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

The recommended durvalumab dose is 1,500 mg every 3 weeks for patients with a body weight ≥ 30 kg when given with gemcitabine and cisplatin, followed by 1,500 mg every 4 weeks as a single agent until disease progression or unacceptable toxicity. For patients with a body weight < 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.

For more information on durvalumab, view the full prescribing information.

U.S. Food and Drug Administration

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