EVITA Criteria to Identify Patients Unfit for EV/Pembro

Enrique Grande, MD, PhD, MSc, of MD Anderson Cancer Center Madrid, and Amanda Nizam, MD, of Cleveland Clinic, discuss the development and implications of criteria for identifying patients ineligible for enfortumab vedotin and pembrolizumab (EV/pembro) in the treatment of metastatic urothelial carcinoma (mUC), emphasizing the need for evolving and consensus-based guidelines.

View their continued comments on EVITA Criteria: Opening Doors for Novel Therapies in EV/Pembro-Ineligible Patients.

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Dr. Nizam: Good morning. I am here with Dr. Enrique Grande, and we are discussing the Letter to the Editor he wrote in response to the EV-302 trial. This letter was published recently in European Urology, detailing criteria for identifying patients who may not be optimal candidates for EV/pembro.

Welcome, Dr. Grande. Could you tell us how this criteria was developed, what specific factors you and your colleagues looked at, and why you developed it?

Dr. Grande: I am delighted to be here, Dr. Nizam. Thank you for the invite. Good morning, everyone. Drs. Ashish Kamat, Alison Birtle, and I discussed the exciting data about the EV-302 trial, which showed that the combination of EV/pembro is changing the natural history of mUC. The progression-free survival, overall survival, and complete response rates are remarkable, making this combination practice-changing. Major guidelines like NCCN and ESMO have already updated their recommendations to include this treatment. However, there are toxicities associated with it, such as neurotoxicity, skin rash, hyperglycemia, and fatigue.

These side effects are common with all oncology drugs, especially with new drug families like antibody-drug conjugates. We questioned whether all patients are suitable candidates for EV/pembro. According to the recent publication by Dr. Tom Powles and colleagues in Annals of Oncology, the vast majority of patients with mUC are fit for this treatment. However, “vast majority” does not mean 100%. We agree that not all patients in oncology can receive the same treatment.

Before EV, we used the Galsky criteria to determine eligibility for cisplatin and the Gupta criteria for platinum eligibility. The EVITA criteria were developed specifically for EV. Although the mechanism of action and toxicities differ from previous drugs, the criteria aim to identify patients who are ineligible due to these toxicities.

Patients are considered ineligible for EV if they meet at least 2 of these 5 criteria: hemoglobin A1c above 8%, glucose levels above 150 mg/dL in 2 consecutive samples 1 week apart, grade 2 sensory or motor neuropathy, retinal abnormalities often related to diabetes, creatinine clearance below 45 mL/min, and an ECOG performance status of 2. Each of these criteria can potentially be managed with active measures, such as controlling glucose levels. The inclusion of creatinine clearance is not due to drug metabolism but to conditions related to uncontrolled diabetes.

This consensus criteria should evolve and gain broader acceptance. We might consider having major and minor EVITA criteria. For example, grade 2 neuropathy alone might not warrant ineligibility, but combined with another minor criterion, it might. We are open to refining these criteria based on broader consensus and practical feedback.

Dr. Nizam: One criterion that stood out to me was the inclusion of corneal or retinal abnormalities. Could you explain why this was included?

Dr. Grande: We included diabetic retinopathy due to its connection with uncontrolled diabetes. Nephritis and creatinine clearance alterations also relate to diabetes. The ECOG performance status is another critical factor, influenced by the tumor’s aggressiveness, disease burden, and comorbidities. This criterion, like the others, requires fine-tuning to reflect the complexities of patient conditions.