Mercinelli Chiara, Moschini Marco, Cigliola Antonio, Mattorre Benedetta, Tateo Valentina, Basile Giuseppe, Cogrossi Laura L, Maiorano Brigida A, Patanè Damiano A, Raggi Daniele, Pastorino Giovanni L, Re Chiara, Colecchia Maurizio, Lucianò Roberta, Colombo Renzo, Brembilla Giorgio, De Cobelli Francesco, Briganti Alberto, Pavlick Dean C, Ross Jeffrey S, Montorsi Francesco, Bellone Matteo, Necchi Andrea
Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
Medical Oncology Unit 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
J Clin Oncol. 2024 Dec 10;42(35):4196-4205. doi: 10.1200/JCO.24.00576. Epub 2024 Sep 6.
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/m 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.
评估纳武利尤单抗联合白蛋白结合型紫杉醇作为新辅助治疗，随后进行根治性膀胱切除术（RC）以及术后辅助使用纳武利尤单抗，用于治疗肌层浸润性膀胱癌（MIBC）患者的活性和安全性。
符合条件的患者东部肿瘤协作组体能状态评分为≤1，处于T2 - 4aN0 - 1M0期，尿路上皮癌组织学类型占比>50%，且不符合或拒绝基于顺铂的化疗。患者接受4个周期的纳武利尤单抗360mg，每3周1次，联合白蛋白结合型紫杉醇125mg/m²，在第1天和第8天各给药1次，每3周重复，随后进行RC，然后辅助使用纳武利尤单抗360mg，每3周1次，共13个周期。主要终点为病理完全缓解（CR）率（ypT0N0）。次要终点为主要病理缓解（ypT≤1N0）、安全性、无事件生存期（EFS）和总生存期。
2021年12月至2023年6月共纳入31例患者；19例（61.3%）为cT2期，2例（6.5%）为N1期，16例（51.6%）为组织学变异型。5例患者（16.1%）因治疗相关不良事件（TRAEs）接受的新辅助治疗疗程少于4个完整疗程。8例患者（25.8%）发生3/4级TRAEs。28例患者接受了RC，3例在临床CR后拒绝RC，接受了膀胱肿瘤再次经尿道切除术（reTURBT）。该试验达到了主要终点：10例患者（32.3%；95%CI，16.7至51.4）达到ypT0N0缓解。将接受reTURBT的患者纳入后，22例（70.9%；95%CI，55至87）达到ypT≤1N0 - x缓解。中位随访12个月（范围5 - 22个月）后，2例患者术后疾病复发。12个月的EFS为89.8%（95%CI，79.5至100）。
据我们所知，NURE - Combo试验的首个结果表明，这种联合方案可扩大免疫化疗在MIBC患者中的治疗机会。
