Efficacy and safety of disitamab vedotin combined with gemcitabine as neoadjuvant therapy for muscle-invasive bladder cancer: A multi-center, single-arm, phase II trial

BackgroundMuscle-invasive bladder cancers (MIBCs) is a group of molecularly heterogonous diseases that could be stratified into subtypes with distinct clinical courses and sensitivities to chemotherapy. Clinical application of molecular subtypes could help in prediction of neoadjuvant chemotherapy responders. Human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) are mutated in multiple cancers including MIBC and are potential therapeutic targets. The optimal perioperative chemotherapy regimen for MIBCs with HER2 positivity is not defined.MethodsA multi-center, single-arm, phase II trial was performed between August 2022 and February 2024. This study enrolled T2-4aN0M0 bladder cancer with HER2 positivity who were ineligible or intolerable to platinum-based chemotherapy. HER2 positivity was defined as a score of 2+ or 3+ on immunohistochemical [IHC] analysis. The patients received three cycles of intravenous gemcitabine 1000mg/m2 and DV 2mg/kg once every 2 weeks before radical cystotomy and lymph node dissection. The primary endpoints were pathologic complete response (pCR). The secondary endpoints were pathological downstaging (pDS), objective response rate (ORR) and safety.ResultsA total of 17 male patients were enrolled, 15 were IHC 2+ and 2 were IHC 3+. After neoadjuvant treatments, two patients (11.76%) achieved clinically complete response, refused radical cystotomy; and 15 patients (88.24%) subsequently underwent radical cystotomy. Of 15 patients, the postoperative pathological results confirmed 46.7% (7/15) of pCR and 53.3% (8/15) of partial reponse. The ORR was 100% (17/17) and the pDS rate was 100%. Median time from the first dose to database cut-off (28, April 2024) was 6.9 (range, 5.3-12.7) months, and the median progression-free survival was not reached. Five patients (29.41%) experienced treatment-related adverse events (TRAEs). No grade ≥3 TRAEs occurred. The most common of any grade TRAEs were rash (11.76%) and fever (17.65%).ConclusionsDV combined with gemcitabine demonstrated efficacy and safety as a neoadjuvant therapy for MIBCs.Clinical trial identificationNCT05723991.Legal entity responsible for the studyTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.FundingRemeGen Co., Ltd.DisclosureAll authors have declared no conflicts of interest.