EVITA Criteria: Opening Doors for Novel Therapies in EV/Pembro-Ineligible Patients

Enrique Grande, MD, PhD, MSc, of MD Anderson Cancer Center Madrid, and Amanda Nizam, MD, of Cleveland Clinic, continue their conversation on the EVITA criteria, including the importance of personalizing treatment to predict and manage toxicity, the role of real-world data from UNITE in refining the criteria, and the challenges community practitioners face in using enfortumab vedotin (EV) due to limited experience and access.

View their previous comments on EVITA Criteria to Identify Patients Unfit for EV/Pembro.

—

Dr. Nizam: One of my interests is better personalizing treatment, especially in relation to treatment-related toxicity. We’re exploring this in UNITE, which you are likely familiar with. We are looking at how to predict toxicity in patients better. This could be an opportunity to collaborate with pharmaceutical partners, analyze data from established trials, and develop risk prediction models for patients at higher risk of neuropathy or skin toxicities, 2 of the most common dose-limiting toxicities. These broad criteria are helpful as guidelines, and as you mentioned, major and minor criteria can assist clinicians in making decisions. Further personalizing with risk prediction models would require extensive prospective data.

With UNITE, we will present data at ESMO on the efficacy of EV in specific populations outlined in these criteria, such as those with uncontrolled diabetes and baseline neuropathy. It will be interesting to see how the drug works in these patients who were excluded from the trial. How do you envision future research addressing current gaps in understanding the EVITA population? Besides examining these patients retrospectively with real-world data, what other methods could we use to understand the drug’s efficacy better?

Dr. Grande: Kudos to what you are doing with UNITE. Real-world data will help fine-tune our understanding of the EVITA population and identify patients who might not be ideal candidates for EV, whether used alone or with pembrolizumab (pembro). An important aspect of the EVITA criteria is identifying this population. Given the high activity of EV/pembro, nobody is brave enough to compare their drug or combination against it. We will not see any prospective phase 2 or 3 trials comparing EV/pembro to other treatments. Defining the EVITA population might open the door for less active but better-tolerated drugs or combinations for patients not suitable for EV/pembro.

Having criteria to identify these patients is crucial for development. It is also beneficial for community practitioners, who might not have extensive experience with EV. They need fixed rules to identify patients at risk of toxicity. Experience with the drug shows that neuropathy can significantly impact quality of life, skin toxicity can be severe in a small percentage of patients, and glucose control is critical to avoid severe hyperglycemia. These insights might not be as evident to community practitioners who treat only a few patients each year. Providing them with clear rules to identify the EVITA-positive population is helpful. Chemotherapy followed by avelumab or chemotherapy with gemcitabine and cisplatin plus nivolumab are good alternatives. Sequential strategies like chemotherapy followed by maintenance therapy and then EV for second or third-line treatment are also worth considering.

Dr. Nizam: I agree, especially regarding the importance of selecting therapies with toxicity and quality of life in mind. This is crucial for community practitioners who may not specialize in bladder, kidney, prostate, and testicular cancers like we do, given that EV is not approved for other cancers at this time.

Dr. Grande: Do you know the exact number of centers participating in the UNITE study?

Dr. Nizam: We currently have 17 sites, all in the US.

Dr. Grande: How many patients were treated with EV?

Dr. Nizam: All the patients in the study were treated with EV. We have around 800 patients in the database, all from major academic centers.

Dr. Grande: In Spain, and likely in US community centers, access to EV is limited, partly due to cost and partly due to the lack of physician experience. Most sites in Spain treat no more than 1 to 4 patients per center, which is not enough to become experts in managing EV toxicity.

Dr. Nizam: Multi-institutional collaborations are crucial as we develop new therapies in urothelial cancer. Dr. Vadim Koshkin deserves commendation for his efforts. We have gathered significant data to complement clinical trial data. Managing toxicity is challenging with retrospective data, but in the absence of other data, especially for populations excluded from clinical trials, it helps augment our understanding.