UNITE Study: Outcomes With SG for Patients with Variant Histologies

A panel discussion, hosted by Vadim Koshkin, MD, brought together different participating clinicians of the UNITE study, a multisite retrospective study of patients with advanced urothelial carcinoma treated with targeted agents, including enfortumab vedotin and sacituzumab govitecan (SG). Different analyses of UNITE patient subgroups were presented as oral abstracts and posters at the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024. Dr. Koshkin was joined by Amanda Nizam, MD; Matthew Campbell, MD, MS; and Omar Alhalabi, MD.

In the final segment of the panel discussion, the outcomes related to SG for patients with variant histologies are highlighted.

View previous segments from the panel discussion.

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Dr. Koshkin: Of course, we have one more study to discuss.

Dr. Nizam: This study is similar to the study that Dr. Campbell talked about in terms of variant histology. We looked at sacituzumab govitecan outcomes in patients with variant histology. We had about 116 patients total. We compared 44 patients with variant histology with any percentage component to 72 patients with pure urothelial histology. Among those 44 patients that had any variant component, 33% had UC predominant, which was over 50% component of urothelial. Then 11 patients had variant predominant, so over 50% of variant histology.

Now, when we looked at that, the observed response rate was 24%. Most interestingly, I thought, was that 94% of these patients had received sacituzumab govitecan post-EV, which was also reassuring. One of the interesting things I noted about the response rate was that we had 8 plasmacytoid patients. Of the 6 that were evaluable, none had responses. That was one that really stood out to me. We had 2 patients with neuroendocrine, and one of them had a response. Though the numbers were small, the plasmacytoid data definitely raised an eyebrow.

In terms of median progression-free survival, it is 3.7 months, and the overall survival is 6.7 months. Again, there seemed to be no differences when we compared pure urothelial and variant histology with any component. Also, there were no differences when we compared the 19 patients with any squamous component to pure urothelial patients. The takeaway from that is that sacituzumab govitecan, even post-EV, appears to be pretty active among different variant components. With greater numbers, it would be interesting to look at the plasmacytoid patients.

Dr. Campbell: I think it really highlights that, as we move forward with this, we are clearly going to be wanting to look at how enfortumab vedotin partners with pembrolizumab and their real-world population. The big question that everyone is going to have is also going to be how agents perform after that combination. How does chemotherapy perform? How do these others perform? I was intrigued that the response rate with sacituzumab govitecan was in the low 20th percentile. My personal clinic experience had not been overly favorable in seeing patients respond. Median PFS was on the short side, under 4 months, and median survival was 6 months. Just to again highlight that this remains a tough space for patients. It could certainly evolve as that potentially becomes more of a second-line treatment option for some, as compared to now a fourth-line treatment in terms of where we looked at it. So, there is a lot of questions, I think, still to be asked about sequence and how drugs perform after EV exposure.

Dr. Nizam: These prospective trials in patients with variant histologies are tough to do, but there are 2 neoadjuvant trials, at least in the muscle-invasive space: accelerated MVAC and pembrolizumab, as well as neoadjuvant sacituzumab govitecan in histology. They are both phase 2 pilot trials, so those will give us some information as they read out over the next few years in terms of outcomes in variant histologies.

Dr. Koshkin: There is so much compelling data. With that, thank you for all your contributions as well as the input today.

Dr. Nizam: Thank you for your leadership.

Dr. Campbell: It is an honor. UNITE is a great program, so I am happy to be part of it.

Dr. Koshkin: We look forward to many future great projects and hopefully additional great data to help patients.