Immunotherapy has been utilized as a treatment for patients with prostate, bladder, and kidney cancer for several years, representing a proven paradigm, notes Robert Dreicer, MD. However, advances for patients with bladder cancer have been exceptionally slow, with the lack of an FDA approval in nearly 20 years.

Potentially transformative phase I data for the anti-PD-L1 therapy MPDL3280A in bladder cancer were presented at the 2014 ASCO Annual Meeting, explains Dreicer. The benefit seen in this study is particularly promising, given the overall poor prognosis for patients with this disease.

In the phase I trial, MPDL3280A was explored in 68 patients with metastatic urothelial bladder cancer who received prior chemotherapy. The objective response rate with MPDL3280A was 43% in PD-L1 positive patients (IHC 2/3). At the time of the data cut-off, 94% of patients had ongoing responses. The most common all-grade adverse events were decreased appetite (12%), fatigue (12%), and nausea (12%).

Based on these data, the FDA granted MPDL3280A a breakthrough therapy designation. A large phase II study is currently enrolling patients with metastatic urothelial bladder cancer. The study will have two cohorts, one for treatment-naive and the other for pretreated patients (NCT02108652).

Given the lack of available therapies for patients with bladder cancer, a well-conducted phase II study could be used for regulatory approval, believes Dreicer. The early breakthrough designation also bodes well for an early approval for MPDL3280A in bladder cancer, based on phase II data, suggests Omid Hamid, MD.