UNITE Study: Design, Patients Sampled, and Outcomes With EV After Switch Maintenance Avelumab

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 first segment of the panel discussion, the design, patients sampled, and outcomes with EV after switch maintenance avelumab are explored.

View more segments from the panel discussion.

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Dr. Koshkin: We are gathered here today with this distinguished panel to discuss some of the findings from the UNITE study presented at this meeting and perhaps to provide a summary of the study. The UNITE study is a retrospective analysis that specifically examines outcomes in patients with metastatic urothelial cancer who have been treated with targeted agents. Initially, it was conceived as a database to evaluate outcomes with enfortumab vedotin, which was approved several years ago. However, we have since broadened our scope to include other targeted agents such as sacituzumab govitecan and erdafitinib. Our primary aim was to assess whether we would observe similar outcomes in real-world settings as those seen in clinical trials with enfortumab vedotin and other targeted agents. Our initial publication, from a couple of years ago, highlighted comparable outcomes with enfortumab vedotin in this real-world patient population.

Furthermore, we aimed to focus on specific subsets of patients, particularly those who may not have been represented in clinical trials, such as patients with specific comorbidities, variant histologies, and other populations. Subsequently, we have explored various other questions, and at this meeting, we presented several abstracts and an oral presentation. Today, we will delve into some of these findings with our distinguished panel.

I will begin by asking Dr. Nizam to provide a summary of her rapid oral abstract presentation on enfortumab vedotin following switch maintenance avelumab.

Dr. Nizam: In this analysis, we investigated outcomes in patients who had received platinum-based chemotherapy followed by maintenance avelumab. These patients were not part of the investigational trial EV-301 that led to its FDA approval. Our study focused on patients who had responded to platinum-based chemotherapy. We identified 49 patients who underwent sequential platinum-based chemotherapy, maintenance avelumab, and then received enfortumab vedotin. We examined the observed response rate, progression-free survival, and overall survival from the start of enfortumab vedotin treatment, as well as overall survival from the start of platinum-based chemotherapy in the overall cohort. Additionally, we analyzed outcomes in subgroups based on the type of platinum-based chemotherapy received, median time on maintenance avelumab, best response to platinum chemotherapy, and Belmont risk score.

In the overall cohort, the observed response rate was 54% among evaluable patients (41 out of 49 patients). In the intention-to-treat population, it was approximately 45%, similar to the 41% observed in the EV-301 trial’s intention-to-treat population. The median progression-free survival was 7 months, and the median overall survival was 13.3 months, again comparable to the EV-301 trial’s figures of 5.6 months and 12.9 months, respectively. Subgroup analysis revealed no significant differences based on the type of platinum therapy used, median time on avelumab, or best response to platinum-based chemotherapy. However, patients with Belmont risk scores of 0 or 1, indicating those without visceral metastases or poor performance status, exhibited better progression-free and overall survival.

Dr. Koshkin: Could you elaborate on why these particular endpoints were chosen for analysis?

Dr. Nizam: Our aim was to determine whether patients receiving this treatment in real-world settings, specifically those who responded to platinum-based chemotherapy, experienced similar outcomes to those who received sequential platinum-based chemotherapy, checkpoint inhibitor therapy, and then enfortumab vedotin.

Dr. Koshkin: What was the median follow-up duration?

Dr. Nizam: It was 8.5 months from the start of treatment.

Dr. Koshkin: Ah, 8.5 months, which, I believe, is relatively short.

Dr. Nizam: Yes, relatively short. Additionally, we observed that the median time on avelumab was shorter than that seen in the JAVELIN Bladder 100 trial. The median time on avelumab in our study was about 3 months, compared to 6 months in the JAVELIN Bladder 100 trial. This disparity may be attributed to the design of the UNITE registry, which captures patients progressing on maintenance avelumab more rapidly over time.

Dr. Koshkin: So, this population may be somewhat different, which could explain some of these figures?

Dr. Nizam: Yes, it is possible that our population is somewhat skewed.

Dr. Koshkin: That clarifies things. If there are no further questions from the panel, I’d like to ask more about…

Dr. Campbell: Actually, I would like to add something. What I find particularly valuable about this study is how it draws upon data from various sites across the US. While many of these sites are academic centers, collaborating allows us to address questions that may be challenging or impossible to explore within the confines of a traditional clinical trial. The typical patient we see in our clinics often doesn’t perfectly match the criteria for a clinical trial. The UNITE effort enables us to analyze populations that truly reflect those encountered in everyday clinical practice. This work, in particular, sheds light on a relevant question, especially with the emergence of combination therapies in the frontline setting and the role of switch maintenance. I am proud to have been involved in this research, and Dr. Nizam, you did an excellent job presenting it today.