UNITE Study: Sequencing Erdafitinib and EV for Patients With FGFR2/3-Altered Disease

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 (EV) and sacituzumab govitecan. 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 third segment of the panel discussion, the potential for sequencing erdafitinib and EV for patients with FGFR2/3-altered disease is considered.

View more segments from the panel discussion.

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Dr. Koshkin: And perhaps with that, we can move on to the final abstract, which Dr. Alhalabi will discuss.

Dr. Alhalabi: Yes, certainly. I would like to address a minor limitation before we proceed. To ensure fairness to the UNITE database, it is essential to note that while it represents a significant collaborative effort from 16 centers, the histologies were not centrally reviewed, thus constituting a limitation we must acknowledge.

Regarding our abstract, we examined a question we believe is pertinent to the field, especially as more therapies emerge in the bladder space, including erdafitinib as a targeted therapy. We analyzed patients within the UNITE database who underwent next-generation sequencing. Out of nearly 600 patients in the database, approximately 450 had next-generation sequencing data contributed by multiple centers. Among these, we focused on the 93 patients harboring FGFR2/3 alterations—a substantial cohort that underscores the value of collaborative research efforts.

Among these 93 patients, the majority had progressed on immunotherapy, with over 90% having received prior immunotherapy and 60% prior platinum-based therapy. We aimed to investigate how outcomes varied based on the sequence of treatment received for their third therapy. Some patients received enfortumab vedotin followed by erdafitinib upon progression, while others received the reverse sequence. Additionally, there were patients who received only enfortumab vedotin without erdafitinib. Notably, we lacked a fourth group—a control group comprising patients who received erdafitinib but not enfortumab vedotin, which would provide valuable insights.

Dr. Koshkin: Of course, the length of follow-up also impacts the analysis, as some patients who received enfortumab alone may eventually transition to erdafitinib.

Dr: Alhalabi: Absolutely, that is an important consideration. In our analysis, our primary endpoint was overall survival, given the limitations regarding response evaluation in this database. We found that among patients who received enfortumab vedotin followed by erdafitinib, the median overall survival was 19 months. Conversely, for those who received the reverse sequence, it was 21 months. The group that received enfortumab alone had a median overall survival of 12 months, underscoring the importance of treatment sequencing.

We conducted a multivariable analysis to adjust for variables such as treatment sequence, presence of visceral metastases, performance status, and BMI. Interestingly, treatment sequence emerged as the most significant factor influencing overall survival.

We also assessed responses to both enfortumab and erdafitinib, finding them to be comparable. Additionally, we examined progression-free survival across the three groups. While we have data for enfortumab, we lack corresponding data for erdafitinib, representing another limitation.

Dr. Koshkin: My key takeaway from this is that for patients with FGFR3 alterations eligible for both erdafitinib and enfortumab, initiating both treatments in some sequence is crucial. Would you agree?

Dr: Alhalabi: Absolutely.

Dr. Koshkin: It seems to reinforce the importance of molecular sequencing, wouldn’t you say?

Dr. Campbell: Indeed. Understanding the molecular landscape early on in a patient’s metastatic course can significantly inform treatment decisions and potentially improve outcomes.