Nab-Paclitaxel Plus Nivolumab Benefits MIBC Outcomes Post-Radical Cystectomy

A combination of nab-paclitaxel (ABX) and pembrolizumab showed promising results for the treatment of urothelial carcinoma (UC) in prior studies.

New findings from the Nure-Combo trial presented by Andrea Necchi, MD, and colleagues at the 2024 American Urological Association Annual Meeting examined the use of ABX with nivolumab followed by radical cystectomy (RC) and adjuvant nivolumab in patients with muscle invasive bladder cancer (MIBC).

The study involved 31 patients with previously untreated MIBC (clinical stage T2-T4a, N0-1, or M0) who were ineligible for or declined cisplatin-based treatment, had an Eastern Cooperative Oncology Group performance status ≤1, and had a predominant (>50%) UC histology.

A total of 31 patients were enrolled between December 2021 and June 2023. A cT3-4 stage was noted in 17 (54.8%) patients, while 14 (45.2%) had cT2, 2 (6.4%) had N1, and 15 (48.4%) had a variant histology component. The primary end point was pathologic complete response rate (ypT0N0). Secondary end points included major pathological response (ypT≤1N0), safety (Common Terminology Criteria for Adverse Events, Version 5.0), and event-free survival (EFS). Tumor biomarkers included comprehensive genomic profiling and circulating tumor DNA (ctDNA) assay.

Each patient was administered 4 cycles of nivolumab 360 mg every 3 weeks with ABX 125 mg/m² on days 1 and 8, followed by RC and then 13 administrations of adjuvant nivolumab 360 mg every 3 weeks.

A total of 4 (12.9%) patients received <4 cycles of neoadjuvant treatment due to treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 4 patients and included neutropenia, asthenia, increased AST/ALT, neurotoxicity, and acute renal failure.

RC was refused by 3 patients, who were offered repeat transurethral resection of bladder tumor prior to maintenance nivolumab after evidence of a negative ctDNA assay and magnetic resonance imaging complete response. In total, 12 (38.7%; 95% CI, 21.8-57.8) patients achieved a ypT0N0 response and 22 (70.9%; 95% CI, 51.9-85.8) achieved a ypT≤1N0 response.

No disease progression occurred during neoadjuvant treatment. After a median follow-up of 10.6 months (IQR: 8-16), 1 patient had partial response; their 12-month EFS was 96.4% (95% CI, 89.9-100). Mean tumor mutation burden was 12.3 mut/Mb for ypT0N0 responders versus 5.8 mut/Mb for nonresponders.

These initial results of the Nure-Combo trial demonstrate the efficacy and safety of ABX with nivolumab as a novel combination for a perioperative strategy in patients with MIBC, providing sustained efficacy after RC.