Treatment Options for Patients Not Eligible for the EV/Pembrolizumab Regimen

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 second segment of the roundtable series, the panel considered treatment options for patients with metastatic urothelial carcinoma who are not eligible for EV/pembrolizumab.

Watch the next segment in this series.

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Dr. Koshkin: For patients not receiving the EV-302 regimen, what other regimens would you consider?

Dr. Sonpavde: I would highlight the Checkmate 901 regimen, the gemcitabine-cisplatin plus nivolumab combination. While it’s not yet FDA approved in the US, we anticipate approval based on regulatory review. This phase 3 trial compared gem-cis alone to gem-cis plus nivolumab in cisplatin-eligible patients, showing positive outcomes in both progression-free survival (PFS; HR, 0.72) and overall survival (OS; HR, 0.78). Notably, gem-cis plus nivolumab demonstrated a 22% complete response rate, doubling that of gem-cis alone. The durability of complete response with gem-cis plus nivolumab, with a median duration of 37 months, suggests the potential for cure in some patients. This raises the question of whether gem-cis plus nivolumab should be considered, especially for those who might achieve a complete response, such as those with lymph node-only disease, although further trial data are needed to identify these patients.

Dr. Koshkin: Do we have any promising biomarkers or indications to select these patients?

Dr. Sonpavde: ERCC2 is a candidate genomic biomarker that has shown promise in predicting pathological complete response (pCR) in the neoadjuvant setting. While not currently utilized due to its limitations, it could be valuable in selecting between EV/pembro and gem-cis plus nivolumab. Additionally, simple clinical markers like lymph node-only disease may also be useful.

Dr. Koshkin: And for cisplatin-ineligible patients, are there alternative regimens besides EV/pembro?

Dr. Grivas: In regions where EV/pembro may not be accessible, the JAVELIN Bladder 100 paradigm remains relevant. This involves carbo-gem followed by maintenance avelumab for patients who show no progression during induction chemotherapy. Long-term follow-up data from phase 3 studies confirm the overall survival benefit without significant detriment to quality of life. However, this option is primarily for patients without access to EV/pembro, highlighting global disparities in treatment accessibility.

Dr. Friedlander: While EV/pembro showed superior outcomes in the EV-302 study, it’s important to note that about 30% of patients in that study received platinum-based chemotherapy followed by avelumab maintenance, suggesting a role for this regimen in cisplatin-ineligible or EV-ineligible patients. Despite newer data favoring EV/pembro, the JAVELIN Bladder 100 paradigm remains a standard of care in certain settings, especially where EV/pembro is unavailable or unaffordable.

Dr. Grivas: The JAVELIN Bladder 100 paradigm is particularly relevant in regions with limited access to EV/pembro. While the EV-302 study demonstrated significant benefits with EV/pembro, the option of maintenance avelumab following chemotherapy remains important for patients in areas with restricted treatment options.

Dr. Friedlander: Agreed. Real-world data also suggest that not all eligible patients receive maintenance avelumab, indicating potential limitations in its widespread use.

Dr. Koshkin: Overall, the data from EV-302 is impressive across various patient subsets, indicating substantial benefit.

Dr. Tawagi: Yes, the benefits of EV/pembro were consistent across all subgroups, including those with liver metastases or upper tract involvement. We eagerly await further details from the published paper, but the current findings are compelling.

Dr. Koshkin: Indeed. I concur with the panel’s assessment.

Dr. Grivas: One question I have is whether the patients in the chemotherapy control arm of EV-302 had access to EV later on. I assume it was minimal.

Dr. Friedlander: Yes, that’s correct. Given the global nature of the EV-302 study and the limited availability of EV during its conduct, very few patients in the control arm likely had access to EV later on. While we await further data from the paper publication, it’s important to note the constraints on EV availability during the study period.