How Will EV, Pembrolizumab Combination Change the Bladder Cancer Treatment Landscape?

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 first segment of the roundtable series, the panel discussed how enfortumab vedotin and pembrolizumab figures to change the bladder cancer treatment landscape.

Watch the next segment in this series.

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Dr. Koshkin: We are here with GU Oncology Now at ASCO GU 2024, and we have a lot of exciting data to discuss, starting with EV-302 and the tremendous difference this study has made. So, let us begin by discussing which patients might be suitable for other regimens besides EV-302, which comprises enfortumab vedotin (EV) and pembrolizumab.

Dr. Grivas: That is a great question. In the US, with access to EV and pembrolizumab, and now with regular approval for this regimen, I believe the majority of patients will likely receive EV/pembro as a frontline treatment. However, there may be patients who cannot tolerate this regimen due to factors such as peripheral neuropathy, liver disease, uncontrolled diabetes, or high obesity. I estimate that about 10% of patients in my practice may not be suitable candidates for EV. For these patients, there needs to be a risk-benefit discussion regarding alternative treatments.

Dr. Friedlander: I completely agree. The data from the EV-302 trial is incredibly strong, showing a doubling of median OS, doubling of PFS, and a 30% complete response rate. These are unprecedented numbers in bladder cancer. While EV/pembro is groundbreaking, we need to consider factors such as peripheral neuropathy and severe diabetes before starting treatment. It is crucial that both patients and community doctors understand the potential side effects and make informed decisions.

Dr. Grivas: What would you recommend for patients with active autoimmune disease who may not be suitable for pembrolizumab?

Dr. Tawagi: That is a great question. There are now prospective trials enrolling patients with a history of autoimmune disease onto immunotherapy trials, which is promising. In my practice, if a patient’s autoimmune disease is well controlled and they are not on immunosuppressants, I would consider immunotherapy, especially if I have a good rapport with the specialist managing their autoimmune condition. While there may be a slightly higher risk of immune-related adverse events, these can generally be managed with steroids.

Dr. Friedlander: It is important to recognize that each autoimmune condition is different, and the approach may vary. Active immunosuppression versus a history of rheumatoid arthritis would lead to different considerations. However, we should exercise caution when using immunotherapy in patients who are actively on steroids due to the potential for adverse events.

Dr. Koshkin: Indeed, over the nearly decade-long use of immunotherapy-based regimens, oncologists have become more comfortable administering these treatments, even to patients with underlying autoimmune conditions. However, it remains an excellent question to consider in individualized treatment decisions.