(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a urothelial carcinoma poster session. Dr. Chiara Mercinelli presented the initial results of NURE-Combo, a phase 2 study of neoadjuvant nivolumab plus nab-paclitaxel followed by postsurgical adjuvant nivolumab in patients with muscle-invasive bladder cancer (MIBC).
Patients with MIBC undergoing a radical cystectomy remain at high-risk of disease recurrence and mortality, despite the availability of numerous neoadjuvant and adjuvant treatment options. Preliminary data suggest that the combination of nab-paclitaxel and pembrolizumab has activity in patients with advanced urothelial carcinoma. In this presentation, Dr. Mercinelli reported the reported results of a single-arm phase 2 trial of combination pembrolizumab + nab-paclitaxel followed by radical cystectomy and adjuvant nivolumab in MIBC patients.
This trial included patients meeting the following eligibility criteria:
- Cisplatin unfit or declined cisplatin-based chemotherapy
- Previously untreated MIBC (cT2-4aN0-1M0, as per CT and MRI scan)
- ECOG performance status of 0 or 1
- Predominant (>50%) urothelial carcinoma histology
Patients were scheduled to receive four cycles of nivolumab 360 mg every 3 weeks + 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/frequency.
The primary endpoint was pathologic complete response (pCR; ypT0N0), with a null hypothesis of a ≤20% pCR and H1 ≥38% (2-stage design). The secondary endpoints included:
- Major pathological response (ypT≤1N0)
- Safety (CTCAE v5.0)
- Event-free survival
- Biomarker analysis (comprehensive genomic profiling, PD-L1 expression, ctDNA monitoring [Signatera]).
The baseline patient characteristics are summarized below. Thirty-one patients have been enrolled between December 2021 and June 2023. 55% of patients had cT3-4 disease and 6.4% had cN1. A variant histology component was present in nearly half (48.4%).
All 31 patients concluded the neoadjuvant therapy and underwent surgery. From a safety standpoint, 4 patients received <4 cycles of neoadjuvant therapy due to Grade 3 treatment-related adverse events.
The median time from treatment initiation to radical cystectomy was 4 months. In total, 12 patients (39%) achieved a pCR, and 22 (73%) had a ≤ypT1N0 response. No disease progression occurred during neoadjuvant treatment. At a median follow-up of 12 months, two patients had disease progression. The 12-months event-free survival was 89%. Of note, three patients (9.6%) had a complete clinical response and were considered candidates for a repeat TURBT only.
Dr. Mercinelli concluded that neoadjuvant nivolumab + nab-paclitaxel, followed by adjuvant nivolumab, is an effective and safe peri-operative strategy in patients with MIBC, with sustained efficacy post-radical cystectomy. These results could expand the chemotherapeutic combination options for cisplatin-ineligible patients.
Presented by: Chiara Mercinelli, MD, Oncology Resident Physician, Medical Oncology Department, IRCCS San Raffaele Hospital, 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 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024