Updated results of a phase I/II study of durvalumab (Imfinzi) in locally advanced or metastatic urothelial carcinoma were reported by Thomas Powles, MD, of Barts Cancer Institute, Queen Mary University of London, and colleagues in JAMA Oncology. Data from the ongoing study supported the recent approval of durvalumab as second-line treatment in this setting on the basis of durable responses.
In the open-label study, 191 patients with disease that had progressed, who were ineligible for, or who had refused prior chemotherapy received durvalumab at 10 mg/kg every 2 weeks for up to 12 months or until disease progression, start of another anticancer therapy, or unacceptable toxicity. Patients had a median age of 67.0 years, 71.2% were male, 71.1% were white, all had stage IV disease, and 99.5% had prior anticancer therapy (including 95.3% with prior platinum treatment).
Responses and Toxicity
As of the update in October 2016, median follow-up was 5.78 months. An objective response was observed in 34 patients (17.8%), including a complete response in 7. Median time to response was 1.41 months. Median duration of response was not reached, with 17 responders (50%) having a response ≥ 6 months and 26 responders (77%) having an ongoing response at data cutoff. Response rates were 27.6% among 98 patients with programmed cell death ligand 1 (PD-L1) high expression status and 5.1% among 79 with PD-L1 low or negative status. Median progression-free survival and overall survival were 1.5 months and 18.2 months, respectively; 1-year overall survival was 55%.
Grade 3 or 4 treatment-related adverse events occurred in 13 patients (6.8%), and grade 3 or 4 immune-mediated adverse events occurred in 4 patients (2.1%). Treatment-related adverse events led to discontinuation of treatment in three patients (1.6%), two of whom died of immune-mediated adverse events (autoimmune hepatitis and pneumonitis).
The investigators concluded: “Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic [urothelial cancer].” ■