The NURE-Combo trial, a single-center phase II study, has revealed promising initial results for a perioperative chemoimmunotherapy strategy involving nivolumab and nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC). The study, published in the Journal of Clinical Oncology, investigated the safety and efficacy of neoadjuvant nivolumab combined with nab-paclitaxel, followed by postsurgical adjuvant nivolumab.
Study Design and Patient Population
The trial enrolled 31 patients with clinical T2-4a N0-1 M0 stage MIBC who were either ineligible for or refused cisplatin-based chemotherapy. Key eligibility criteria included an Eastern Cooperative Oncology Group performance status score of 0-1 and confirmed urothelial carcinoma histology (>50% of the tumor sample). The treatment regimen consisted of four cycles of nivolumab (360 mg every 3 weeks) plus nab-paclitaxel (125 mg/m2 on days 1 and 8 of each 3-week cycle), followed by radical cystectomy and 13 cycles of adjuvant nivolumab at the same dose and frequency. A significant portion of the enrolled patients presented with aggressive disease characteristics, with 61.3% having clinical T2 stage and 6.5% having N1 stage disease. Furthermore, over half of the patients (51.6%) exhibited variant histology, which is often associated with poorer outcomes.
Efficacy Outcomes
The primary endpoint of the study was the pathologic complete response rate (ypT0N0). Secondary endpoints included major pathologic response (ypT1N0 or less), event-free survival, and safety. Of the 31 patients enrolled, 28 underwent radical cystectomy, while three patients who achieved a clinical complete response opted for a redo transurethral resection of the bladder tumor (TURBT) instead. The study met its primary endpoint, with 32.3% (95% CI, 16.7 to 51.4) of the intention-to-treat population achieving a ypT0N0 response. When including the patients who underwent redo TURBT, the rate of ypT1N0-x or less was 70.9% (95% CI, 55 to 87). At a median follow-up of 12 months (range, 5-22 months), the 12-month event-free survival rate in the intention-to-treat population was 89.8% (95% CI, 79.5 to 100), with only two patients experiencing a relapse after radical cystectomy.
Safety Profile
All patients completed the neoadjuvant phase of the trial, proceeding to either radical cystectomy or redo TURBT. However, 16.1% of patients received fewer than four full courses of neoadjuvant therapy due to treatment-related adverse events. The most frequently reported nonhematologic treatment-related adverse events were gastrointestinal disorders (45.2%), followed by asthenia (38.7%), paresthesia (29.0%), and increased transaminase (22.6%). Grade 3 treatment-related adverse events included neutropenia (9.7%), acute renal injury (6.4%), anemia (3.2%), asthenia (3.2%), increased transaminase (3.2%), and cutaneous toxicity (3.2%). Overall, grade 3 treatment-related and immune-related adverse events were observed in 25.8% and 12.9% of patients, respectively. Notably, no treatment-related adverse events of grade 4 or higher were reported.
Clinical Implications
The investigators concluded that the NURE-Combo trial provides insights into the potential value of expanding chemotherapy combinations with immune checkpoint inhibitors in early-stage muscle-invasive bladder cancer. This approach was deemed medically and surgically safe in a population with a high unmet medical need. The early efficacy signals, coupled with the characteristics of included patients, suggest an opportunity to replace cisplatin chemotherapy as backbone therapy for unselected patients. According to Michael A. Carducci, MD, FACP, FASCO, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, the combination of nivolumab and nab-paclitaxel appears efficacious when looking at complete pathologic response as its endpoint, yet it requires confirmation in subsequent studies.
Andrea Necchi, MD, of IRCCS San Raffaele Hospital, Milan, emphasized the need for validation in larger cohorts and ongoing research on tumor and liquid biomarkers to further enhance the benefit provided to patients, with the goal of achieving a bladder-intact event-free survival whenever a clinical complete response is observed after the preoperative window.
