The FDA has approved durvalumab (Imfinzi®, AstraZeneca UK Limited) in combination with gemcitabine and cisplatin for treatment of locally advanced or metastatic biliary tract cancer.
"Biliary tract cancer, a heterogeneous group of malignancies that includes intrahepatic and extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer, is typically diagnosed at advanced stages, for which curative surgery is not feasible and prognosis is poor," wrote Do-Youn Oh, MD, PhD, Professor of Medical Oncology at the Seoul National University Hospital, Seoul National University College of Medicine, and colleagues in their publication of the TOPAZ-1 trial (NCT03875235), on which approval was based. "First-line standard of care for advanced disease (gemcitabine and cisplatin chemotherapy) has remained unchanged for the past decade."
The phase 3, multi-regional, double-blind trial randomized 685 patients with intrahepatic cholangiocarcinoma (56%), gallbladder cancer (25%), or extrahepatic cholangiocarcinoma (19%) in a 1:1 ratio to receive either 1,500 mg of durvalumab in combination with 1,000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin, or placebo plus the identical dosage of gemcitabine and cisplatin. Treatment was measured on a 21-day cycle for up to eight cycles, during which durvalumab or placebo was administered intravenously on Day 1 followed by gemcitabine and cisplatin, which were administered on Days 1 and 8. Following completion of gemcitabine and cisplatin treatment, durvalumab or placebo were administered once every four weeks until disease progression or unacceptable toxicity. The primary end point measured was overall survival, with key secondary end points of progression-free survival and overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using investigator assessment.
At a median follow-up of 16.8 months in the durvalumab arm and 15.9 months in the placebo arm, overall survival was significantly extended in those receiving durvalumab, at a median of 12.8 months compared with those receiving the placebo, who had a median of 11.5 months. Investigator-assessed median progression-free survival was 7.2 months in the durvalumab arm compared with a median of 5.7 months in the placebo arm. In addition, investigator-assessed overall response rate was found to be 27% in the durvalumab arm compared with 19% in the placebo arm.
The most common adverse events seen in ≥20% of patients receiving durvalumab were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.
"A trend toward overall and progression-free survival benefit with durvalumab and chemotherapy was observed across all subgroups analyzed," concluded Dr. Oh and colleagues in their report. "In conclusion, the global, phase 3 TOPAZ-1 trial, at a preplanned interim analysis, met the primary objective of a statistically significant improvement in overall survival in patients with advanced biliary tract cancer."
The recommended dosage of durvalumab for patients weighing ≥30 kg is 1,500 mg every three weeks in combination with gemcitabine and cisplatin, followed by 1,500 mg every four weeks by itself until disease progression or unacceptable toxicity. The recommended dosage of durvalumab for patients weighing <30 kg is 20 mg/kg every three weeks plus gemcitabine and cisplatin, followed by 20 mg/kg every four weeks until disease progression or unacceptable toxicity.
For More Information
US Food and Drug Administration (2022). FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer?utm_medium=email&utm_source=govdelivery
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