Metastatic bladder cancer treatments take step forward with immunotherapy

Almost half of patients with metastatic bladder cancer only surviving nine months after receiving the first line of treatment with cisplatin-based chemotherapy. Now, with work on different therapies to extend lives, researchers have found that immunotherapies may be provide viable options in both first and second line treatments after two phase II clinical trials.

The two clinical trials included the phase II KEYNOTE-052 trial to test the efficiency and safety of PD-1 blockade with pembrolizumab as a first line treatment in patients with metastatic bladder cancer, and the phase II CheckMate 275 trial that analyzed the PD-1 inhibitor nivolumab in bladder cancer patients who have experienced cancer progression after receiving first line platinum-based chemotherapy.

Of the 100 patients enrolled in the KEYNOTE-052 trial, the endpoint response rate was measured to be 24 percent. The biomarker cut point, which measured the number of patients expected to respond to the treatment, was 10 percent or greater, meaning patients had to present a minimum of 10 percent total number of PD-L1 that showed in either immune or tumor cells. The study found that 30 patients had this level of PD-L1, 11 of whom responded to treatment.

"Pembrolizumab has substantial activity with a favorable safety profile as first line therapy in cisplatin ineligible patients with metastatic bladder cancer,” said Arjun Balar, MD, assistant professor at New York University's Langone Medical Center. “The biomarker cut point will need to be validated in the larger study population, but seems to identify patients most likely to respond to pembrolizumab well. Immunotherapy is rapidly redefining our treatment approach for patients facing this dreadful disease."

The second phase II trial (CheckMate 275) focused on the efficiency of immune checkpoint blockades such as the PD-1 inhibitor nivolumab. The study found that, in the 265 patients enrolled in the study who had progressed even after undergoing platinum-based chemotherapy, the objective response rate of 19.6 percent was beyond the expectations of researchers in patients with both high and low levels of PD-L1.

"This year the first immune check point inhibitor, atezolizumab, was approved for patients with bladder cancer and CheckMate 275 provides similar results with nivolumab in the second line setting," said Maria De Santis, associate clinical professor at the University of Warwick, U.K. "Immune check point inhibitors have started to alter the therapeutic landscape for bladder cancer. We expect even more dramatic changes in the coming years with the use of immunotherapy in other clinical stages and as combination therapy."