The FDA has granted an accelerated approval to the PD-L1 inhibitor durvalumab (Imfinzi) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
A complementary diagnostic for PD-L1, the VENTANA PD-L1 (SP263) Assay, was simultaneously approved.
The approval was based on a single-arm trial that included 182 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression following platinum-containing chemotherapy. Patients received durvalumab at 10 mg/kg IV every 2 weeks.
The objective response rate (ORR) per blinded independent central review was 17.0% (95% CI, 11.9-23.3). At the data cutoff, the median duration of response was not reached (range, 0.9+ to 19.9+ months).
Using the VENTANA PD-L1 (SP263) Assay, response was also evaluated by PD-L1 status. Among 95 patients with high PD-L1 expression the ORR was 26.3% (95% CI, 17.8-36.4). In the cohort of 73 patients with low or no PD-L1 expression, the ORR was 4.1% (95% CI, 0.9-11.5).
All grade adverse events (AEs) occurring in 15% or more of patients included fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection.
Grade 3/4 AEs occurred in 43% of patients. Infection and immune-related AEs observed with durvalumab included pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, and diabetes.
In February 2016, the FDA granted a breakthrough therapy designation to durvalumab as a treatment for patients with PD-L1–positive inoperable or metastatic urothelial bladder cancer following progression on prior treatment with a platinum-based regimen.
The accelerated approval of durvalumab in bladder cancer is contingent upon results from a confirmatory trial.
Durvalumab is also being evaluated as a single agent and in combination with tremelimumab in the phase III DANUBE trial in the frontline setting for patients with metastatic urothelial carcinoma, regardless of their eligibility for cisplatin-based chemotherapy.
More than 30 other ongoing trials are evaluating various combinations of durvalumab with other immunotherapies and targeted agents.