After decades without any significant advances in the treatment of bladder cancer, a number of recently completed and ongoing clinical trials of immunotherapy agents are changing the landscape of bladder cancer treatment, according to Peter Black, MD, FACS, FRCSC, who discussed the latest research during a Monday morning plenary presentation.
“This is a burgeoning and rapidly changing field, with several new agents to help reactivate the antitumor immune response currently under clinical development. The amount of information coming out of these trials is sometimes hard to keep up with,” said Dr. Black, a Urologic Oncologist at Vancouver General Hospital, a Research Scientist at the Vancouver Prostate Centre and associate professor in the Department of Urologic Sciences at the University of British Columbia, Canada.
Among the studies Dr. Black discussed was a phase 3 trial of 500 patients with recurrent bladder cancer who were randomized to either pembrolizumab or to “dealer’s choice” chemotherapy.
“This is some of the most advanced data that we currently have,” Dr. Black said. “The primary end point was overall survival and this study has suggested that there’s a clear benefit to pembrolizumab with respect to overall survival and also with progression-free survival, although it’s worth noting that in the first four months of treatment there might be a response benefit to chemotherapy. Perhaps most intriguing, however, is the durability of response with immunotherapy.”
Pembrolizumab is not approved by the U.S. Food and Drug Administration. However, data from other phase 2 and phase 3 trials have led to the approval of four drugs, including two approvals in the past two weeks.
“The latest news was just last week when there was a press release regarding a phase 3 trial very similar to the pembrolizumab trial. But this time it was atezolizumab that failed to meet its primary end point of overall survival,” Dr. Black said. “We don’t really know why at this point. We know that the atezolizumab arm performed as expected, but the chemotherapy arm performed better than expected, so we have to await further data.”
With regard to first-line therapy, Dr. Black touched on recent studies looking at patients who had received prior chemotherapy.
“There are data in cisplatin-ineligible patients — patients with renal dysfunction or poor performance status — who have been treated with different regimens of chemotherapy,” he said. “In these patients you can expect a response rate of about one-third and a mean overall survival of about nine months. The atezolizumab trial looking at this reported a somewhat lower objective response rate, but better durability of response and improved overall survival. This was a single-arm trial, so we’re comparing cross-trials, but it does look promising.”
Based on data from that trial, atezolizumab was recently approved by the FDA for first line treatment in cisplatin ineligible patients.
Other trials to test the efficacy of checkpoint blockade in first line, platinum-eligible patients are ongoing, and the optimal sequencing of chemotherapy and immunotherapy will be addressed in the near future, Dr. Black said.
“The other natural development occurring with checkpoint blockade is its migration into earlier disease states,” he added. “Trials are under way to test these agents before and after radical cystectomy for muscle invasive bladder cancer.”
Dr. Black said three of the agents are also being tested in patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer, with the intent of avoiding cystectomy and preserving the bladder.
“Immunotherapy in bladder cancer is a very exciting field with a lot of promise, but it also is a work in progress,” Dr. Black said. “It’s up to us as urologists to push these therapies and get these trials done.”