The Food and Drug Administration has granted accelerated approval to the checkpoint inhibitor durvalumab for patients with locally advanced or metastatic urothelial carcinoma who have disease progression after prior treatment with a platinum-containing chemotherapy.
The agency also approved a complementary diagnostic for the assessment of the PD-L1 protein the tumor tissue.
Approval was based on an objective response rate (ORR) of 17% (95% confidence interval, 11.9-23.3) in a single-arm trial of 182 patients with locally advanced or metastatic urothelial carcinoma whose disease progressed following platinum-containing chemotherapy. Durvalumab, 10 mg/kg, was administered intravenously every 2 weeks. The median response duration was not reached at data cutoff (range, 0.9+ months to 19.9+ months). Confirmed ORR was 26.3% (95% CI, 17.8-36.4) in 95 patients with a high PD-L1 score and 4.1% (95% CI, 0.9-11.5) in 73 patients with a low or negative PD-L1 score, according to a statement from the FDA.
The most common adverse reactions were fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection. Pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, and diabetes also occurred in patients taking durvalumab.
The recommended dose of durvalumab is 10 mg/kg IV over a period of 60 minutes, every 2 weeks, until disease progression or unacceptable toxicity occurs. Full prescribing information is available here .
Durvalumab is marketed as Imfinzi by AstraZeneca. The complementary diagnostic is the Ventana PD-L1 (SP263) Assay from Ventana Medical Systems.