Editorial Comment

Abstract

For the urologic oncology community, the massive unmet need for therapeutics in bladder cancer throughout the disease spectrum is widely recognized. For patients with non–muscle-invasive bladder cancer (NMIBC), this issue is best illustrated by the following: 3 drug approvals in 30 years, in contrast to 5 new drugs approved for castration-resistant metastatic prostate cancer in the last 3 years. There are many reasons for this dismal performance, including limited interest by big (and little) pharma and a rather poor track record of completion of clinical trials in urothelial cancer. NMIBC is inherently problematic to study in the context of clinical trials in no small part because of a lack of consensus on trial end points both from a clearly clinical and regulatory perspective. The present report summarizes the work at a joint Food and Drug Administration and American Urological Association meeting, whose goal was to reach some consensus on potential trial designs and end points, to “jump start” efforts for the development of novel therapeutics. The focus, appropriately, was on both high-risk NMIBC and BCG-refractory carcinoma in situ (CIS). For the latter setting, there appeared to be broad consensus that there is no standard comparator for a randomized trial, and perhaps of more importance, that an initial complete response rate of 40%-50% at 6 months and a durable response rate of at least 30% for 18-24 months, with the lower bound of the 95% confidence interval excluding 20% could be clinically meaningful – which I interpret to mean as a potentially approvable endpoint. With respect to trial design for patients with high-risk NMIBC, there was consensus that the preferred primary endpoint for these trials should be time to event, using failure to achieve a complete response in patients with CIS and recurrence in patients with CIS or papillary disease as the events. This joint effort of the American Urological Association and Food and Drug Administration is encouraging but requires follow-up action from the urologic oncology community to “encourage” our colleagues in pharma to explore this area of unmet need with renewed enthusiasm, especially given a potential window of opportunity for drug development in trials with end points that are more broadly accepted, which could potentially lead to regulatory approval. Clinical Trial Design for the Development of New Therapies for Nonmuscle-invasive Bladder Cancer: Report of a Food and Drug Administration and American Urological Association Public WorkshopUrologyVol. 83Issue 2PreviewTo summarize the discussion at a public workshop, cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association, reviewing potential trial designs for the development of new therapies for non–muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for NMIBC in the last 30 years, and product development for this disease has been stymied by difficulties in trial design and patient accrual. Full-Text PDF