PADCEV (enfortumab vedotin-ejfv) as a monotherapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy has been approved by Astellas Pharma Inc. and Seagen Inc., according to preliminary results from Cohort H of the EV-103 trial. On February 18, data from this late-breaking abstract will be presented orally at the ASCO Genitourinary Cancers Symposium (ASCO GU) in 2022.
MIBC is a stage of bladder cancer in which the tumour has migrated into the bladder wall muscle. MIBC is usually treated with cisplatin-based chemotherapy, as well as radical cystectomy, or bladder removal, and pelvic lymph node dissection. Patients with MIBC who were eligible for surgical treatment but not for cisplatin-based chemotherapy were enrolled in Cohort H of the Phase 1b/2 EV-103 study. On days one and eight of each three-week cycle, patients received three cycles of neoadjuvant (pre-surgery) enfortumab vedotin.
The preliminary review of 22 patients found that 36.4 percent had a pathologic complete response, or no evidence of cancer on microscopic examination of tissue cells removed after surgery, which was the primary outcome. A secondary goal of the trial was histological downstaging, or a reduction in tumour size, which was achieved in half of all patients (50 percent). Following therapy with enfortumab vedotin, all patients had surgery, and no procedures were postponed. Fatigue (45.5 percent), alopecia (36.4 percent), dysgeusia (36.4 percent), diarrhoea (27.3 percent), nausea (27.3 percent), peripheral sensory neuropathy (27.3 percent), dry eye (22.7 percent), and rash maculo-papular (22.7 percent) were the most common adverse events (AEs) associated with treatment with enfortumab vedotin, all of which were consistent with the known safety profile of enfortumab vedotin.
“Neoadjuvant cisplatin-based chemotherapy, which is intended to shrink tumors prior to surgery, prolongs survival in patients with MIBC. However, up to half of these patients with MIBC are ineligible for cisplatin treatment and typically must undergo surgery without that treatment,”said Ahsan Arozullah, M.D., M.P.H., Vice President, Medical Sciences-Oncology, Astellas.
“Results from EV-103 Cohort H showed that, when patients received enfortumab vedotin prior to surgery, more than one-third displayed no evidence of cancer when their bladder was removed and examined microscopically for residual tumors. After treatment with enfortumab vedotin, all patients proceeded to surgery. Given there is no standard of care for neoadjuvant treatment in cisplatin-ineligible patients, these results are important and support further research,”said Daniel Petrylak, M.D.
“The initial findings from EV-103 Cohort H are encouraging, and we look forward to learning more from the Phase 3 studies evaluating enfortumab vedotin in muscle-invasive bladder cancer in combination with the anti-PD-1 therapy pembrolizumab,”said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development at Seagen.