FDA Grants Enfortumab Vedotin Breakthrough Designation for Urothelial CarcinomaJonathan Rosenberg, MD • OncologyJun 18, 2018 Op-Med is a collection of original articles contributed by Doximity members.</iframe</p> <p><p><i><a href="https://www.doximity.com/profiles/51d2d736-8321-42d2-adf9-647ae5404ab0">Dr. Jonathan E. Rosenberg</a> presented on updates in Genitourinary Oncology at the meeting. Below is the full transcript of the interview.</i></p></p> <p><p><strong>Rosenberg:</strong> We have the development of antibody drug conjugates, which are novel therapies of an antibody conjugated to cytotoxic agents. It’s targeted specifically to cancer cells, releases the payload in the cancer cells, and I would describe it as a targeted chemotherapy. I mean these often have a better safety profile than systemic cytotoxic chemotherapy. And there’s emerging data suggesting that some of these drugs have substantial activity in urothelial cancer, particularly a treatment called enfortumab vedotin, which is being tested in patients with metastatic urothelial cancer, who progressed after checkpoint inhibitors. </p></p> <p><p>The data reported in ASCO at this meeting is very exciting in terms of high levels of response compared to standard therapies that might be for those patients. The drug has actually gotten breakthrough therapy status by the FDA in the United States for the treatment of urothelial cancer. Hopefully, over the next couple of years, we'll see the drug approved for the treatment of this disease in patients who had prior immunotherapy. </p></p> <p><p>We're also very interested in combinations of immunotherapy and bladder cancer for patients who have stage 4 disease. We know that the outcomes in a select group are quite good, but for the majority of patients the outcomes unfortunately are not. We need to have a multi-pronged approach with a background, most likely of checkpoint inhibition with PD-1 or PD-L1 therapy, but also incorporating novel agents. </p></p> <p><p>So, we have a program testing multiple new approaches—either by targeting the fibroblast growth factor receptors, targeting carbon emission, targeting angiogenesis—to see whether these different pathways make a difference and boost response rates immunotherapy of bladder cancer. </p></p> <p><p>There are multiple different approaches urothelial in around the world. We hope that some of these will lead to substantial improvements and outcomes without substantial toxicity. </p></p> <p><p><strong>Doximity: Immunotherapy has been transformative, but recent setbacks lead people to question if the field is moving too quickly… What are your thoughts on these developments and where the field is headed?</strong></p></p> <p></p><strong>Rosenberg:</strong> There are recent data that were released by the independent data monitoring committees and two randomized phase three trials of immune checkpoint therapy, either as monotherapy in combination with chemotherapy, or chemotherapy by itself. The data safety monitoring committees noted that patients who were at low levels of PD-L1 expression had inferior outcomes in terms of survival compared to those with high PD-L1 expression on the monotherapy arms. </p></p> <p><p>So patients that I recommended those trials stopped accrual to PD-L1 low monotherapy with PD-L1 low monotherapy with the checkpoint inhibitor. This is essentially scrambling the field right now because many clinical trials and many patients are receiving treatment with PD-L1 or PD-1 monotherapy in the first-line setting and now without any restriction on PD-L1 status. </p></p> <p><p>We need to rethink how we're thinking about these patients. Perhaps bladder cancer is more like lung cancer where first line, single agent checkpoint therapy really requires high level of PD-L1 expression in order for it to be highly active. We didn't see that in the original study as to the degree that it apparently is the case in the randomized phase 3 trials—of course that's why we do randomized phase 3 trials to prove these points.</p></p> <p><p>Right now, I think it's a period of reflection and trying to understand this data and see how it will impact things. In Europe, the EMA has restricted the availability of immune checkpoint therapy and first-line bladder cancer based on PD-L1 stating. In the United States, the FDA as of today has not done that, but that may be coming in the near future. </p></p> <p><p>So this is a sea change for us in bladder cancer where we could put PD-L1 stating to the side and say it's not really relevant. In the second line setting, it doesn't appear to be relevant, but it sounds like the first line setting in fact it is and we need to pay attention to that.</p></p> <div class="editorial-disclaimer">All opinions published on Op-Med are the author’s and do not reflect the official position of Doximity or its editors. Op-Med is a safe space for free expression and diverse perspectives. 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