ASCO GU Urothelial Cancer Study Roundup: EV, Atezolizumab, Erdafitinib, and More

A roundtable discussion, moderated by Vadim Koshkin, MD, discussed the post-EV-302 world for metastatic urothelial carcinoma, as well as recent trial data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024. Dr. Koshkin was joined by Petros Grivas, MD, PhD; Karine Tawagi, MD; Terence Friedlander, MD; and Guru Sonpavde, MD.

In the sixth segment of the roundtable series, the panel considered the latest available data pertaining to EV, atezolizumab, erdafitinib, and other therapy options.

Watch the next segment in this series.

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Dr. Koshkin: I will briefly mention another abstract, which was an analysis of the UNITE study, presented as one of the Rapid Oral presentations by Dr. Amanda Nizam. This abstract examined the activity of EV in patients who had received switch maintenance avelumab therapy.

These patients had previously undergone platinum-based chemotherapy and experienced clinical benefit, such as a response or stable disease, making them eligible for switch maintenance avelumab. Subsequently, upon progression on switch maintenance avelumab, they received EV. This represents a somewhat different population from the one in which EV was approved as monotherapy, specifically comprising patients who had progressed on platinum-based chemo and then received an immune checkpoint inhibitor.

What we observe in this abstract is that the outcomes align with expectations for EV. The retrospective study showed response rates just above 50%, approximately 54%, with a median progression-free survival (PFS) of around 7 months and an overall survival of about 13 months. These findings are consistent within this patient population, emphasizing that even with the approval of EV/pembro and many patients receiving that combination, EV can still be used as monotherapy in this treatment setting.

Now, I would like to pivot to another abstract that Dr. Sonapvde may elaborate on. There were a couple of compelling abstracts on combination therapy.

Dr. Sonpavde: Following the DAD trial, which we presented at ESMO, demonstrating a combination of 2 ADCs for the first time, EV and sacituzumab, with a 70% response rate, there were a couple of other combinations discussed at this meeting.

One is the combination of cabozantinib plus pembrolizumab in the first-line setting for cisplatin-ineligible PD-L1 high patients. These patients were either platinum ineligible or refusing platinum-based therapy. In this study, cabozantinib was combined at a daily dose of 40 mg with pembrolizumab.

This was a small study with approximately 36 evaluable patients, and the response rate was close to 46 percent, with a complete response rate of around 14 to 15 percent. It is worth noting that this study contrasts with the lenvatinib plus pembrolizumab first-line trial, which was negative compared to pembrolizumab alone, largely due to its poor patient population with 80% of patients at PS2, mostly platinum ineligible.

Another combination worth mentioning is the one involving EV and erdafitinib, studied in patients with FGFR2/3 activating mutations or fusions. This phase 1 study included data on 8 patients and demonstrated tolerability with the expected toxicities associated with both agents.

All 8 patients showed a partial response, which is promising, although the small sample size necessitates further investigation into safety and efficacy with a larger patient cohort. Questions arise regarding the potential of combining EV/pembro with erdafitinib or utilizing erdafitinib in switch maintenance therapy alongside pembro, possibly omitting EV after around 6 months.

Dr. Friedlander: Are you concerned about the skin toxicity associated with the combination of EV and erdafitinib?

Dr. Sonpavde: Yes, but we need more data on this. Erdafitinib is not highly skin toxic, though skin toxicities can occur. EV, on the other hand, raises concerns, so careful monitoring is necessary.

Dr. Koshkin: A lot of compelling data there, especially regarding these newer combinations.