A phase 2 trial of risk enabled therapy after neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer (RETAIN-2).

作者：Pooja Ghatalia, Eric A. Ross, Matthew R. Zibelman, Fern Anari, Philip H. Abbosh, William Tester, Tracy L. Rose, Suzanne Cole, James Ryan Mark, Rosalia Viterbo, Erika Jerome, Eric M. Horwitz, M.A. Hallman, Andres Correa, Marc C. Smaldone, Robert G. Uzzo, David YT Chen, Alexander Kutikov, Elizabeth R. Plimack, Daniel M. Geynisman · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.5_suppl.815 · 被引用次数：29 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Tea Polyphenols and Effects

815 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or chemoradiation (CRT) is the standard of care for patients (pts) with muscle invasive bladder cancer (MIBC). Mutations in DNA damage repair genes enrich for pathologic downstaging after NAC. In RETAIN-1, a risk-adapted approach was employed to identify patients for cystectomy-sparing active surveillance (AS) following NAC, reporting a 73% 2-year MFS rate. RETAIN-2 employs a similar approach but incorporates neoadjuvant chemoimmunotherapy. Methods: This is a phase II, multi-institutional trial in which pts with cT2-T3N0M0 MIBC, ECOG PS 0-1 and CrCl≥50 mL/min received neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) with nivolumab. Pre-NAC transurethral bladder resection (TURBT) specimens were sequenced for mutations (pathogenic or VUS) in ATM , ERCC2 or RB1 . Pts with >1 mutation and clinical complete response (cCR) post-NAC (based on restaging TUR, urine cytology and CT imaging) initiated active surveillance (AS). Remaining pts underwent bladder-directed therapy: intravesical therapy (< cT2 post-NAC), CRT or RC. The primary endpoint is 2-year metastasis-free survival (MFS) for ITT pts which is not mature. This interim analysis reports clinically meaningful secondary endpoint outcomes. Results: A total of 80 pts were treated over 40 months at four academic centers and 71 were evaluable per protocol. The median age was 69 years (range: 66-86)...