Efficacy and Safety of Disitamab Vedotin Combined with Gemcitabine as Neoadjuvant Therapy in Muscle-invasive Bladder Cancer: An Open-label, Multicenter, Single-arm, Phase 2 Trial.

There are barriers to the clinical use of cisplatin-based neoadjuvant regimens in muscle-invasive bladder cancer (MIBC), especially for patients with renal dysfunction, hearing loss, heart diseases, or other severe comorbidities. Favorable efficacy and safety of disitamab vedotin (DV), an antibody-drug conjugate targeting HER2, have recently been demonstrated in urothelial carcinoma. We explored neoadjuvant gemcitabine combined with RC48 in the MIBC setting. Initially, 26 patients with clinical stage T2-4a Nx M0 MIBC and a HER2 immunohistochemical expression score of 2+/3+ were enrolled. The neoadjuvant regime comprised DV (2 mg/kg intravenous infusion, day 1) and gemcitabine (1000 mg/m2 intravenous infusion, day 2) in a 14-d cycle. Thirteen patients received three cycles, and the other 13 patients received four cycles, in a nonrandomized manner. Subsequently, 22 patients underwent radical cystectomy (RC). Postoperative pathology revealed a pathological complete response (pCR) rate of 59% (13/22) among RC patients, 40% (4/10) of whom had received three cycles and 75% (9/12), four cycles. Intention-to-treat analysis revealed pCR rates of 50% (13/26) overall, 31% (4/13) for the three-cycle group, and 69% (9/13) for the four-cycle group. At median follow-up of 16.9 mo, 25 patients remained event-free. Treatment-related adverse events primarily included aspartate aminotransferase elevation (35%), alanine aminotransferase elevation (38%), a decrease in appetite (23%), alopecia (23%), and sensory neuropathy (23%). Validation of the long-term efficacy of this regimen is required.