Earlier this week, the U.S. Food and Drug Administration (FDA) announced that it had approved a new immune checkpoint inhibitor, durvalumab (Imfinzi), for the treatment of certain patients with the most common form of bladder cancer—urothelial carcinoma. Specifically, the FDA approved durvalumab for 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.
According to the FDA announcement, the approval was based on results from a phase II clinical trial that showed that 17 percent of the 182 patients who received durvalumab had a partial or complete response. At the most recent analysis, the median duration of the responses had not been reached.
Among the 95 patients whose tumors were found to have high levels of the protein PD-L1 on the surface when analyzed using the VENTANA PD-L1 (SP263) Assay, the overall response rate was 26 percent. In contrast, the overall response rate was just 4 percent among those patients whose tumors had low levels of PD-L1, as assessed using the assay. Given these data, the FDA approved the VENTANA PD-L1 (SP263) Assay as a complementary diagnostic for use in assessing levels of PD-L1 protein on urothelial carcinoma tissue. This means that physicians are not required to use this test before treating urothelial carcinoma patients with durvalumab, but they may wish to use the information it provides when advising patients about treatment options.
Given that the approval of durvalumab is based on response data, rather than overall survival, durvalumab’s manufacturer, AstraZeneca, is required by the FDA to conduct additional studies to confirm that the immune checkpoint inhibitor improves survival for patients with urothelial carcinoma.
Immune checkpoint inhibitors are a class of immunotherapeutics that work by releasing brakes on cancer-fighting immune cells called T cells. Durvalumab targets the protein PD-L1, which normally engages a T-cell brake called PD-1. Once the PD-1 brake is released by durvalumab, the T cells are able to destroy cancer cells.
Durvalumab is the third 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. As discussed on this blog, nivolumab (Opdivo), which targets PD-1, and atezolizumab (Tecentriq), which targets PD-L1, were approved for the same use in February 2017 and May 2016, respectively.
Two other immune checkpoint inhibitors that target the PD-1/PD-L1 braking system, pembrolizumab (Keytruda) and avelumab (Bavencio), are under review at the FDA for use as a treatment for urothelial carcinoma. Therefore 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.
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