FDA Approves Durvalumab for Advanced Urothelial Carcinoma

The FDA also approved the Ventana SP263 assay for the assessment of PD-L1 tumor status

The US Food and Drug Administration (FDA) has approved the PD-L1–blocking monoclonal antibody durvalumab (Imfinzi) for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed on or following treatment with platinum-containing chemotherapy, either in the neoadjuvant or adjuvant setting.

The FDA also approved a PD-L1 diagnostic, the Ventana SP263 assay, for the assessment of PD-L1 tumor status in these patients, though testing is not required for use of durvalumab.

“Patients who have disease progression during or following chemotherapy are left with few other treatment options,” said Nicholas J. Vogelzang, MD, of the University of Nevada School of Medicine and Comprehensive Cancer Centers of Nevada, in a press release. “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.”

Durvalumab received approval based on the results of Study 1108, a single-arm phase I/II trial that included 182 patients with either locally advanced urothelial carcinoma or metastatic disease whose cancer progressed after treatment with platinum-containing chemotherapy. The agent was given at 10 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

Results of the trial showed an objective response rate of 17% (95% CI, 11.9–23.3) in all patients, regardless of PD-L1 status, with partial responses in 26 patients and complete responses in five patients. Among responders, 14 had ongoing responses of 6 months or longer and five had ongoing responses of 12 months or longer.

In patients (n = 95) with high PD-L1 expression as measured by the Ventana SP263 assay, the objective response rate was 26.3% (95% CI, 17.8–36.4). In patients with low/negative PD-L1 expression the response rate was 4.1% (95% CI, 0.9–11.5).

The agent is currently being tested as a first-line treatment for urothelial carcinoma in the phase III DANUBE trial, either as a monotherapy or in combination with the anti–CTLA-4 agent tremelimumab.

Common adverse events (AEs) in the trial (> 15% of patients) were constipation, decreased appetite, fatigue, musculoskeletal pain, urinary tract infection, nausea, and peripheral edema, with serious AEs occurring in 46% of patients. The most frequent serious AEs (> 2%) were acute kidney injury (4.9%), musculoskeletal pain (4.4%), urinary tract infection (4.4%), general physical health deterioration (3.3%), liver injury (3.3%), abdominal pain (2.7%), pyrexia (2.7%), and sepsis (2.7%).

Eight patients (4.4%) who were treated with durvalumab died, and three other patients were experiencing infection and disease progression at the time of death.

Infection and immune-related AEs such as adrenal insufficiency, colitis, diabetes, hepatitis, pneumonitis, and thyroid disease were also seen in durvalumab-treated patients.