FDA Approves Durvalumab Plus Chemo for Biliary Tract Cancer

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The US Food and Drug Administration (FDA) has approved durvalumab (Imfinzi) for use in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancer.

The drug, an immune checkpoint inhibitor that targets programmed cell death-ligand 1 (PD-L1), is already approved for use in patients with lung cancer.

The approval for the new indication of biliary tract cancer is based on data from the TOPAZ-1 trial, the agency noted in its announcement.

Results from this trial were presented at the Gastrointestinal Cancers Symposium organized by the American Society of Clinical Oncology (ASCO) earlier this year, as reported at the time by Medscape Medical News.

“TOPAZ-1 is the first phase 3 trial to show that adding immunotherapy to standard chemotherapy can increase survival in biliary tract cancer, and importantly, does so without inducing any new serious side effects,” said lead author Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology at Seoul National University Hospital and Seoul National University College of Medicine, Korea.

The combination represents a new standard of care, suggested Cathy Eng, MD, a US expert commenting on the findings who was speaking as an ASCO expert in gastrointestinal cancers.

Trial Conducted Across Many Countries

This trial involved 685 patients with histologically confirmed locally advanced unresectable or metastatic biliary tract cancer who had not previously received systemic therapy for advanced disease. Among these patients, 56% had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma.

It was conducted across many countries in Europe, South America, and Asia, as well as the United States. The FDA noted that trial demographics were as follows: 56% Asian persons, 37% White persons, 2% Black persons, and 4% persons of other race; 7% Hispanic or Latino persons; 50% men and 50% women; median age, 64 years (range, 20-85 years); and 47% aged 65 years or older.

All patients received chemotherapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of each 21-day cycle for up to eight cycles.

In addition, they were randomized to also receive immunotherapy (durvalumab 1500 mg) or placebo on day 1 followed by the same dose every 4 weeks.

Durvalumab or placebo was continued until disease progression or unacceptable toxicity. Treatment was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit, as determined by the investigator, the agency noted.

The results showed a statistically significant improvement in overall survival for patients who received immunotherapy in addition to chemotherapy.

The median overall survival was 12.8 months with durvalumab vs 11.1 months with placebo (hazard ratio, 0.80; P = .021).

The median progression-free survival was 7.2 months with durvalumab vs 5.7 months with placebo.

Investigator-assessed overall response rate was 27% with durvalumab vs 19% with placebo.

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

The agency noted that the recommended durvalumab dosage is 1500 mg every 3 weeks for patients with a body weight ≥ 30 kg when given with gemcitabine and cisplatin, followed by 1500 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.

The full prescribing information for durvalumab is available here.

The FDA noted that the review for this indication was conducted under Project Orbis and that the agency collaborated with the Australian Therapeutic Goods Administration, Health Canada, Singapore’s Health Sciences Authority, and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies.

This application was also granted priority review and orphan drug designation.

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