FDA Approves Durvalumab Combined With Gemcitabine and Cisplatin for Biliary Tract Cancer

The Food and Drug Administration (FDA) granted approval to durvalumab, an IgG1 monoclonal antibody that has high-affinity binding to PD-L1 receptor, in combination with gemcitabine and cisplatin to treat adult patients with locally advanced or metastatic biliary tract cancer. Durvalumab was previously approved for treatment of patients with unresectable Stage 3 non-small cell lung cancer whose disease has not progressed following concurrent chemoradiotherapy and, in combination with etoposide and either carboplatin or cisplatin, as a first-line treatment for adult patients with extensive-stage small cell lung cancer.

The current approval was based on the double-blind, multi-regional, international phase 3 TOPAZ-1 trial, which enrolled 685 patients with locally advanced unresectable or metastatic biliary tract cancer who had not previously received systemic therapy for advanced disease. Of all the patients, 56% had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma.

The TOPAZ-1 trial randomized patients on a 1:1 basis to either 1500 mg durvalumab on Day 1 plus 1000 mg/m² gemcitabine and 25 mg/m² cisplatin on Days 1 and 8 of each 21-day cycle for up to 8 cycles, followed by 1500 mg durvalumab monotherapy once every 4 weeks, or placebo on Day 1 plus gemcitabine and cisplatin on Days 1 and 8, followed by placebo once every 4 weeks. The primary outcome was overall survival (OS), with progression-free survival (PFS) and overall response rate (ORR) included in the secondary outcomes.

There was a statistically significant improvement in the OS of those patients in the durvalumab group compared to those in the placebo group. The median OS was 12.8 months (95% confidence interval [CI], 11.1 to 14) in the durvalumab group and 11.5 months (95% CI, 10.1 to 12.5) in the placebo group (hazard ratio, 0.80; 95% CI, 0.66 to 0.97; P = .021). The median PFS was 7.2 months (95% CI, 6.7 to 7.4) in the durvalumab group, compared to 5.7 months (95% CI, 5.6 to 6.7) in the placebo group. In the durvalumab group, the ORR was 27% (95% CI, 22% to 32%), compared to 19% (95% CI, 15% to 23%) in the placebo group.

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

Source:

FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. United States Food and Drug Administration. September 2, 2022. Accessed September 6, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer