(UroToday.com) The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to an abstract session for surgical, non-surgical, and systemic treatment options for patients with localized, muscle-invasive bladder cancer (MIBC). Dr. Chiara Mercinelli presented the first results of NURE-Combo, a phase 2 trial of neoadjuvant nivolumab plus nab-paclitaxel followed by adjuvant nivolumab in patients with MIBC.
MIBC remains a systemic disease with a high risk of recurrence following radical cystectomy. Data from the phase II PEANUT study have suggested that nab-paclitaxel is active in combination with pembrolizumab in patients with advanced urothelial carcinoma.1 NURE-Combo is a phase 2, single arm trial of neoadjuvant nivolumab plus nab-paclitaxel followed by adjuvant nivolumab in patients with MIBC.
The study eligibility criteria were as follows:
- Cisplatin unfit or declined cisplatin-based treatment
- Previously untreated MIBC (cT2-4aN0-1M0, per conventional imaging [CT or MRI scan])
- ECOG performance status 0–1
- Predominant (> 50%) urothelial carcinoma histology
Patients received 4 cycles of nivolumab 360 mg every 3 weeks plus nab-paclitaxel 125 mg/m2 on days 1 and 8 of every 3-week cycle, followed by radical cystectomy. Patients received adjuvant nivolumab 360 mg every 3 weeks.
The primary endpoint was the pathologic complete response rate (ypT0N0). The investigators proposed a null hypothesis of a complete response rate of ≤20%, with the null hypothesis rejected if the complete response rate was ≥38% (two-stage design; ≥9 ypT0N0 were required in stage 1+2).
Secondary endpoints included the following:
- ‘Major’ pathologic response, defined as ≤ypT1N0
- Event-free survival
- Safety, defined using the CTCAE v5.0 criteria
Evaluable tumor biomarkers included comprehensive genomic profiling (CGP) and PD-L1 expression and circulating tumor DNA monitoring (Signatera).
Baseline patient characteristics are summarized below (n=31). The median patient age was 65 years. 52% had pure urothelial carcinoma 55% had cT3-4 disease and 6.5% had clinical node-positive disease. The median duration from the 1st cycle of systemic therapy to surgery was 4 months. 87% of patients received all 4 cycles of neoadjuvant nab-paclitaxel + nivolumab. All patients were able to proceed to surgery safely.
Thirty-one patients were enrolled between December 2021 and June 2023. A pathologic complete response was achieved in 12 patients (39%; 95% CI: 22 to 56%), whereas 22 patients (73.3%, 95% CI: 55 to 87%) achieved a ≤ypT1N0 response. Three patients (10%) experience a clinical complete response and were candidates for a re-TURBT only.
None of the patients experienced disease progression during neoadjuvant treatment; however, at a median follow-up of 12 months, two patients experienced disease progression. The 12-months event-free survival was 89%.
There were no significant associations between comprehensive genomic profiling results and pathologic responses:
Multivariable analysis evaluating predictors of achieving a pathologic complete or ‘major’ response demonstrated that only older age was predictive of increased odds of achieving a ‘major’ pathologic response. All other assessed clinicopathologic variables were negative.
The most observed any-grade hematologic adverse events were anemia (65%) and neutropenia (19%). The most common non-hematologic events included gastrointestinal events (45%), asthenia (39%), and cutaneous toxicity (36%). Treatment-related serious adverse events occurred in 10% of patients.
The investigators concluded that nivolumab plus nab-paclitaxel is an effective and safe perioperative strategy in patients with MIBC, with sustained efficacy post-radical cystectomy.
These results could expand the opportunities of chemotherapy combinations in cisplatin-ineligible patients. They argued that these results further strengthen the role of clinical complete response in ‘envisioning’ organ-sparing approaches.
Presented by: Chiara Mercinelli, MD, Oncology Resident Physician, Università Vita-Salute San Raffaele, Milan, Italy
Written by: Rashid Sayyid, MD, MSc - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024
Reference:
- Giannatempo P, Raggi D, Marandino L, et al. Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study. Ann Oncol. 2020;31(12):1764-72.