Dr Gupta on the 4-Year Efficacy of the EV-103 Trial in Urothelial Carcinoma

Shilpa Gupta, MD, director, Genitourinary Medical Oncology, Taussig Cancer Institute, co-leader, Genitourinary Oncology Program, Cleveland Clinic, discusses the 4-year safety and efficacy data derived from the phase 1/2 EV-103 trial (NCT03288545) in patients with locally advanced or metastatic urothelial carcinoma.

At the 2023 ASCO Annual Meeting, Gupta and colleagues presented data from a median follow-up of 47 months for patients enrolled in dose escalation and cohort A of EV-103, which examined frontline enfortumab vedotin-ejfv (Padcev) combined with pembrolizumab (Keytruda). Findings showed that the overall response rate was 73.3% (95% CI, 58.1%-85.4%) per blinded independent central review, and there was a concordance rate of best overall response of 95.3% between BICR and investigators assessments. The median overall survival (OS) and progression-free surrvial per BICR review were 26.1 months (95% CI, 15.51–not estimable [NE] and 12.7 months (95% CI, 6.11-NE), respectively . Notably, the tail of the OS and PFS curves have both plateaued, indicating that this regimen has demonstrated long-term efficacy, Gupta says.

Moreover, investigators did not observe any new safety signals with additional follow-up, Gupta expands. The most common toxicities associated with the combination were peripheral neuropathy, rash, and fatigue, she says. Although these toxicities were reversible and resolved, patients receiving this regimen need to be monitored for these adverse effects, Gupta notes.

If a rash appears within the first few cycles of treatment, it can be resolved quickly with decreasing the dose, or a discontinuation or break from treatment, Gupta continues. Peripheral neuropathy was observed later during treatment and took a median of 7.2 months to resolve, which can be disabling for patients, she explains. Therefore, it is important to know how the patient feels after each cycle and determine if they are developing any new symptoms, she says. Additionally, hyperglycemia was another adverse effect that could occur earlier in the treatment course, and this can also resolve with adequate supportive measures and dose reductions, Gupta concludes.