EV-103 Cohort L: Investigating Enfortumab Vedotin as SOC for Cisplatin-Ineligible MIBC

In patients with muscle-invasive bladder cancer (MIBC), the current standard of care (SOC) includes neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND). For patients who are ineligible for cisplatin-based treatments, the SOC is RC+PLND alone, and adjuvant therapy may also be recommended; however, high rates of recurrence still remain in this patient population.

Cohort L of the EV-103 study sought to examine the efficacy of enfortumab vedotin as a perioperative treatment for cisplatin-ineligible patients with MIBC. Initial results of the cohort were presented at the European Society for Medical Oncology Congress 2023 by Dr. Srikala Sridhar, of the University of Toronto.

The cohort enrolled patients with previously untreated MIBC who were cisplatin-ineligible and agreed to undergo curative intent RC+PLND within 12 weeks. Patients were administered 3 cycles of neoadjuvant enfortumab vedotin (1.25 mg per kg) on days 1 and 8 of each 3-week cycle followed by RC+PLND, and then 6 cycles of adjuvant enfortumab vedotin (1.25 mg per kg) on days 1 and 8 of every 3-week cycle beginning 8 weeks post-RC.

The primary end point was pathological complete response (pCR), and secondary end points included pathological downstaging (pDS) rate, safety, and tolerability.

A total of 52 patients were enrolled, and 51 patients were treated with enfortumab vedotin in the neoadjuvant phase with a median of 3 cycles. RC+PLND was completed by 42 (82.4%) patients. One patient achieved complete response and opted not to undergo RC+PLND.

A total of 17 patients (34%) had a pCR, while pDS occurred in 21 (42%) patients. The most common treatment-related adverse events (TRAEs) were fatigue (52.9%), maculo-papular rash (31.4%), and nausea (29.4%). Enfortumab vedotin-related TRAEs grade 3 or higher occurred in 39.2% of patients, while RC-related TRAEs grade 3 or higher occurred in 31.4%. One patient (2%) experienced an enfortumab vedotin-related death (Stevens-Johnson syndrome) before surgery.

Enfortumab vedotin shows promising activity and tolerability in cisplatin-ineligible patients with MIBC, and the new data support ongoing phase 3 trials evaluating enfortumab vedotin with pembrolizumab for MIBC.