To evaluate the activity and safety of nivolumab with nab-paclitaxel as neoadjuvant therapy, followed by radical cystectomy (RC) and postsurgical adjuvant nivolumab in patients with muscle-invasive bladder cancer (MIBC).
Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤1 and a T2-4aN0-1M0 stage with >50% urothelial carcinoma histology and were ineligible for or refused cisplatin-based chemotherapy. Patients received four cycles of nivolumab 360 mg once every 3 weeks + nab-paclitaxel 125 mg/m2 once on days 1 and 8, every 3 weeks, followed by RC, and then adjuvant nivolumab 360 mg once every 3 weeks × 13 cycles. The primary end point was the pathologic complete response (CR) rate (ypT0N0). Secondary end points were major pathologic response (ypT≤1N0), safety, event-free survival (EFS), and overall survival.
Thirty-one patients were enrolled from December 2021 to June 2023; 19 (61.3%) had a cT2 stage, two (6.5%) had N1 stage, and 16 (51.6%) had a variant histology. Five patients (16.1%) received less than four full courses of neoadjuvant treatment because of treatment-related adverse events (TRAEs). Grade 3/4 TRAEs occurred in eight patients (25.8%). Twenty-eight patients underwent RC, and three refused RC after evidence of clinical CR and received a redo transurethral resection of the bladder tumor (reTURBT). The trial met its primary end point: 10 patients (32.3%; 95% CI, 16.7 to 51.4) achieved an ypT0N0 response. By including those who underwent reTURBT, 22 (70.9%; 95% CI, 55 to 87) achieved an ypT≤1N0-x response. After a median follow-up of 12 months (range, 5-22), two patients had a disease relapse after surgery. The 12-month EFS was 89.8% (95% CI, 79.5 to 100).
To our knowledge, the first results from NURE-Combo trial suggest that this combination could expand the therapeutic opportunities of immune-chemotherapy in patients with MIBC.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Sep 06 [Epub ahead of print]
Chiara Mercinelli, Marco Moschini, Antonio Cigliola, Benedetta Mattorre, Valentina Tateo, Giuseppe Basile, Laura L Cogrossi, Brigida A Maiorano, Damiano A Patanè, Daniele Raggi, Giovanni L Pastorino, Chiara Re, Maurizio Colecchia, Roberta Lucianò, Renzo Colombo, Giorgio Brembilla, Francesco De Cobelli, Alberto Briganti, Dean C Pavlick, Jeffrey S Ross, Francesco Montorsi, Matteo Bellone, Andrea Necchi
Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy., Department of Urology, IRCCS San Raffaele Hospital, Milan, Italy., Cellular Immunology Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy., Vita-Salute San Raffaele University, Milan, Italy., Department of Pathology and Laboratory Medicine, IRCCS San Raffaele Hospital, Milan, Italy., Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy., Foundation Medicine, Inc, Cambridge, MA.