The evolving landscape of bladder cancer treatment, marked by an increasing array of therapeutic options, has created a pressing need for clinical trials to address key unanswered questions, particularly concerning the sequencing of immune checkpoint inhibitors. Petros Grivas, MD, PhD, of the University of Washington Medicine and Fred Hutchinson Cancer Center, emphasized the necessity of trials to determine the optimal strategies for utilizing these agents.
The Checkpoint Inhibitor Rechallenge Question
A critical area of uncertainty revolves around rechallenging patients with checkpoint inhibitors like nivolumab and pembrolizumab after they have previously received these drugs in the adjuvant or neoadjuvant setting. The question is whether these agents can be effectively used again upon metastatic recurrence. Data from kidney cancer trials, specifically CONTACT-03 (NCT04338269) and TiNivo-2 (NCT04987203), suggest that rechallenging with checkpoint inhibitors after prior exposure may not provide significant benefit. However, Dr. Grivas noted the importance of conducting dedicated trials in bladder cancer to validate these findings in the urothelial carcinoma setting.
Sequencing Challenges with Novel Therapies
Beyond the rechallenge question, other sequencing dilemmas are emerging. One such challenge involves determining the appropriate treatment course following pembrolizumab in combination with enfortumab vedotin. Additionally, the optimal sequencing of therapies involving erdafitinib, particularly in patients harboring FGFR alterations, requires further investigation.
The Role of Germline Mutation Testing
Furthermore, research into driver mutations in bladder cancer has underscored the significance of germline mutation testing. This testing, coupled with genetic counseling, can identify patients and families who may benefit from cancer prevention screening and early detection efforts. The identification of germline mutations can have implications not only for the patient but also for their broader family, enabling proactive measures to mitigate cancer risk.
"I think this is really showing the interest that bladder cancer as a disease has attracted over the last decade. With more therapy options for our patients, there are many unanswered questions, and that's why we need clinical trials to answer those questions," said Dr. Grivas. He also noted the importance of next-generation sequencing in determining the optimal sequencing of therapies.
