Based on the first results of the single-center phase II NURE-Combo trial, which were reported in the Journal of Clinical Oncology (JCO) by Mercinelli et al, the combination of neoadjuvant nivolumab plus nab-paclitaxel followed by postsurgical adjuvant nivolumab appeared to be safe and active in patients with muscle-invasive bladder cancer.
“This single-arm study shares significant insight into a novel non–cisplatin-based combination in the neoadjuvant muscle-invasive bladder cancer setting,” commented JCO Associate Editor Michael A. Carducci, MD, FACP, FASCO, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. “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.”
Study Details
A total of 31 patients who met the following criteria were eligible to enroll in the study:
- Eastern Cooperative Oncology Group performance status score of up to 1
- Clinical T2–4a N0–1 M0 stage
- Confirmed pure or predominant (> 50% of the tumor sample) urothelial carcinoma histology
- Planned for radical cystectomy but ineligible for or refused cisplatin-based chemotherapy.
They were administered 4 cycles of 360 mg of nivolumab every 3 weeks plus 125 mg/m2 of nab-paclitaxel on days 1 and 8 of each 3-week cycle, followed by radical cystectomy and 13 cycles of adjuvant nivolumab at the same dose level and frequency. A total of 61.3% and 6.5% of the population had clinical T2 and N1 stage disease, respectively. More than half of patients (51.6%) had a variant histology.
Pathologic complete response (ypT0N0) was evaluated as the primary endpoint. Secondary endpoints included major pathologic response (ypT1N0 or less), event-free survival, and safety.
Efficacy Findings
A total of 28 patients underwent radical cystectomy. Three patients who showed evidence of a clinical complete response declined the procedure and instead underwent a redo transurethral resection of the bladder tumor (TURBT).
A total of 32.3% of the intention-to-treat population achieved a ypT0N0 response. Including the patients who underwent a redo TURBT, the rate of ypT1N0-x or less was 70.9%.
At a median follow-up of 12 months (range = 5–22 months), two patients experienced a relapse after radical cystectomy. The 12-month event-free survival rate in the intention-to-treat population was 89.8%.
Safety Summary
All patients completed the neoadjuvant phase and proceeded to either radical cystectomy or redo TURBT. However, 16.1% received fewer than four full courses of neoadjuvant therapy because of treatment-related adverse events.
Gastrointestinal disorders were the most frequently reported nonhematologic treatment-related adverse events (45.2%), followed by asthenia (38.7%), paresthesia (29.0%), and increased transaminase (22.6%). The following grade 3 treatment-related adverse events were documented: 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. No treatment-related adverse events of grade 4 or higher were reported.
KEY POINTS
- The NURE-Combo trial met its primary endpoint of ypT0N0 responses with a perioperative chemoimmunotherapy approach in patients with muscle-invasive bladder cancer.
- The combination demonstrated a manageable overall safety profile.
- The use of chemotherapy agents, in combination with immune checkpoint inhibitors, may be expanded beyond platinum therapy while preserving or potentially improving efficacy.
The investigators concluded: “The NURE-Combo trial provided insights into the potential value of expanding chemotherapy combinations with immune checkpoint inhibitors in the setting of early-stage muscle-invasive bladder cancer. This approach was medically and surgically safe in a population with a high unmet medical need, and the early efficacy signals, coupled with the characteristics of included patients, suggested an opportunity to replace cisplatin chemotherapy as backbone therapy for unselected patients.”
They added: “While these results certainly need validation in larger cohorts, ongoing research on tumor and liquid biomarkers could further enhance the benefit provided to the patients, with the goal of achieving a bladder-intact event-free survival, which seems possible and safe whenever a clinical complete response is deemed after the preoperative window.”
Andrea Necchi, MD, of IRCCS San Raffaele Hospital, Milan, is the corresponding author of the JCO article.
DISCLOSURE: The study was funded by Bristol Myers Squibb and the Associazione Italiana per la Ricerca sul Cancro. For full disclosures of the study authors, visit ascopubs.org.
