KEY TAKEAWAYS
- The NURE-Combo phase 2 trial aimed to investigate the efficacy and safety of neoadjuvant NIVO combined with nab- ABX, followed by RC and adjuvant NIVO in patients with MIBC.
- The primary endpoint was to determine PCR.
- Researchers concluded that the NURE-Combo trial demonstrated the potential effectiveness and safety of the novel chemo-immunotherapy combination NIVO+ABX in MIBC patients.
Muscle-invasive bladder cancer (MIBC) is a systemic disease with a high recurrence risk post-radical cystectomy (RC), the standard of care (SOC) for cisplatin-ineligible patients. Preliminary findings indicate nab-paclitaxel (ABX’s) activity in combination with pembrolizumab for advanced urothelial carcinoma. Chiara Mercinelli and her team aimed to present the phase 2 trial results of neoadjuvant nivolumab (NIVO + ABX) followed by RC and adjuvant NIVO in MIBC patients.
Researchers conducted an inclusive analysis involving eligible patients unfit for cisplatin or those who declined cisplatin-based treatment with previously untreated MIBC meeting clinical criteria (T2-T4a, N0-1, M0 via CT and MRI scan). Criteria included Eastern Cooperative Oncology Group performance status ≤ 1 and predominant (> 50%) urothelial carcinoma histology. Patients underwent 4 cycles of NIVO 360 mg Q3W + ABX 125 mg/m2 on Day 1 and 8, Q3W, followed by RC. Adjuvant NIVO was administered for 13 cycles. The primary endpoint was the pathologic complete response (pCR) rate ypT0N0; H0: ≤20% and H1≥ 38% in a 2-stage design: ≥9 ypT0N0 were required in stage 1+2). Secondary endpoints encompassed major pathological response (ypT≤1N0), safety (CTCAE v5.0), and event-free survival (EFS). Tumor biomarkers included comprehensive genomic profiling (CGP), PD-L1 expression, and circulating tumor DNA monitoring (Signatera).
About 31 patients were enrolled in the study between December 2021 and June 2023, with 17 (54.8%) at cT3-4 stage, 14 (45.2%) at cT2, 2 (6.4%) at N1 stage, and 15 (48.4%) exhibiting variant histology. All 31 patients completed neoadjuvant treatment, and as of the data cutoff, 29 showed pathological responses. 4 patients (14.8%) received <4 cycles due to treatment-related adverse events (TRAEs), with 4 experiencing G3 TRAEs, including neutropenia (2), asthenia (1), increased AST/ALT (2), neurotoxicity (1), and acute renal failure (1). The median time from treatment start to RC was 4 months (IQR: 3-4).
A total of 11 patients (38%; 95%CI 20.3-55.6) achieved ypT0N0 response, and 21 (72%; 95%CI 55.3-88.3) achieved ypT≤1N0 response. No disease progressions (PD) occurred during neoadjuvant treatment. After a median 10.6 months follow-up (IQR: 8-16), only 1 patient experienced PD, resulting in a 12-month event-free survival (EFS) of 96.4% (95%CI: 89.9-100). The mean tumor mutational burden (TMB) was 12.3 mut/Mb for ypT0N0 responders versus 5.8 mut/Mb for non-responders. Notably, all patients with MRI complete response (CR) had a ctDNA-negative assay post neoadjuvant NIVO-ABX.
The study concluded that the Nure-Combo trial highlights the potential of the novel chemo-immunotherapy combination NIVO+ABX as an effective and safe perioperative strategy for MIBC patients, offering sustained efficacy post-RC. These findings may broaden the scope of chemotherapy combinations for cisplatin-ineligible patients and underscore the significance of clinical CR in advocating for organ-sparing approaches.
The Study is sponsored by IRCCS San Raffaele
Source: https://meetings.asco.org/abstracts-presentations/229753
Clinical Trail: https://clinicaltrials.gov/study/NCT04876313
Mercinelli C, Basile G, Raggi D, et al. (2024). “First results of NURE-Combo: A phase 2 study of neoadjuvant nivolumab (NIVO) and nab-paclitaxel (ABX) followed by postsurgical adjuvant NIVO in patients (pts) with muscle-invasive bladder cancer (MIBC).” Presented at ASCO GU 2024 (Abstract 610).
