On May 1, 2017, the FDA accelerated the approval of durvalumab (Imfinzi; AstraZeneca) for the treatment of locally advanced or metastatic urothelial carcinoma in patients whose disease progressed during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment. On the same day, the FDA approved the Ventana PD-L1 Assay as a complementary diagnostic test to assess PD-L1 levels in urothelial carcinoma tissue.
“The usual course of treatment for patients with advanced bladder cancer begins with a standard platinum-containing chemotherapy. Patients who have disease progression during or following chemotherapy are left with few other treatment options. The approval of Imfinzi to treat this population of select patients signifies hope for those who are currently suffering, or may find themselves with limited options in the future,” said Nicholas J. Vogelzang, MD, FACP, FASCO, Clinical Professor, University of Nevada School of Medicine.
The FDA also granted durvalumab priority review and breakthrough therapy designation for this indication.
This approval was based on a single-arm clinical trial involving 182 patients with locally advanced or metastatic urothelial carcinoma that progressed after previous platinum-containing chemotherapy. Of the 182 patients, 95 had high PD-L1 levels. The median follow-up time was 5.6 months. The overall response rate was 17% in all patients, 26.3% in patients with high PD-L1 expression, 21.4% in patients with PD-L1 expression that was not evaluable, and 4.1% in patients with low or no PD-L1 expression.
The median duration of response was 12.3 months in patients with low or no PD-L1 expression and was not reached in patients with high PD-L1 expression, and patients whose PD-L1 was not evaluable.
The most common (≥15%) all-grade adverse reactions included fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection. Grade 3 or 4 adverse events were reported in 43% of patients who received durvalumab, including pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, and diabetes.