Another Immunotherapy Approved for Bladder Cancer

Avelumab is the fourth immune checkpoint inhibitor to get FDA approval to treat certain patients with bladder cancer.

In the spring of 2016 there were no immune checkpoint inhibitors approved by the U.S. Food and Drug Administration (FDA) for treating the most common form of bladder cancer – urothelial carcinoma.

avelumab bladder cancer
Image via National Cancer Institute

The recent approval of avelumab (Bavencio) increased the number of checkpoint inhibitors approved for bladder cancer to four, with a fifth under review. These revolutionary immunotherapeutics have been added to the armamentarium for oncologic urologists treating patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed despite treatment with platinum-based chemotherapy or whose disease progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy.

The FDA’s approval was based on results from a phase II clinical trial that showed that 16 percent of the 162 patients who had been followed for at least six months after starting avelumab treatment had a partial or complete response. At the most recent analysis, the median duration of the responses had not been reached. The FDA also noted that 6 percent of patients died due to an adverse reaction and 41 percent of patients had serious adverse reactions.

Because the approval was based on response data, rather than overall survival, avelumab’s manufacturer, EMD Serono, is required by the FDA to conduct additional studies to confirm that the immune checkpoint inhibitor improves survival.

The importance of confirmatory studies is particularly pertinent given a recent announcement from Roche, the manufacturer of another immune checkpoint inhibitor approved for bladder cancer, atezolizumab, which revealed that atezolizumab did not significantly improve overall survival for patients compared with chemotherapy in its confirmatory phase III IMvigor211 clinical trial. What this means for the status of atezolizumab as a treatment for urothelial carcinoma is not yet known, but the community awaits the FDA review of the data and its subsequent decision about this.

Immune checkpoint inhibitors are a form of immunotherapeutic that work by releasing brakes on cancer-fighting immune cells called T cells. Avelumab targets the protein PD-L1, which normally engages a T-cell brake called PD-1. Once the PD-1 brake is released by avelumab, the T cells can destroy cancer cells.

Avelumab is the fourth immune checkpoint inhibitor that targets the PD-1/PD-L1 braking system to be approved by the FDA for treating certain patients with urothelial carcinoma. Another checkpoint inhibitor is being reviewed for the treatment of bladder cancer. It is hoped that this revolutionary group of immunotherapies will provide benefit to more and more bladder cancer patients like Dave Maddison, who was featured in the AACR Cancer Progress Report 2016.