1620P - A phase II study of perioperative nalirifox in patients with resectable pancreatic ductal adenocarcinoma (rPDAC): Survival update and biomarkers analysis of the NITRO trial

Background

The risk of positive surgical margins, poor recovery after surgery that impairs postoperative treatments, and a high risk of recurrence might limit the current standard treatment for rPDAC. This study evaluated the safety and the activity of perioperative liposomal irinotecan 50 mg/m² + 5-FU 2400 mg/m² + LV 400 mg/m² + oxaliplatin 60 mg/m² (NALIRIFOX) for patients with rPDAC.

Methods

nITRO was an investigator-initiated, Simon’s two-stages, single arm study. Eligible patients had newly diagnosed rPDAC with <180° interface with major veins’ wall and a Karnofsky status ≥60. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, day 1 and 15 of a 28 day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. Plasma concentration of 25 different cytokines was measured by a multiplex xMAP/Luminex technology.

Results

107 patients were enrolled and began preoperative treatment (ITT population). 9 patients discontinued the treatment in the preoperative phase because of treatment related or unrelated adverse events (AEs). The disease control rate was 92.9%. 87 (81.2%) patients underwent surgical exploration, 11 (10.3%) had intraoperative evidence of unresectable or metastatic disease, and 1 died due to surgical complications. 49 patients achieved an R0 resection, accounting for a rate of 65.3%, which largely exceeded the alternative hypothesis of 55%. The most common grade >3 AEs were neutropenia and diarrhea (10.3% and 13.1% in the preoperative, 10.2% and 5.1 in the postoperative phase). With an updated median follow-up time of 33·1 months (IQR 23·1-43·6), the median overall survival (OS) of the ITT population was 32.3 months (95% CI 27.8-44.3). The median disease-free and OS of resected patients were 19.3 (95% CI 12.6-34.1) and 44.3 months (95% CI 33.2-NA), respectively. TNF-α, a potent activator of the chemoresistance pathway TAK1/NF-κB, was the circulating factor most significantly correlated with response and survival outcomes.

Conclusions

NALIRIFOX was manageable and active for patients with rPDAC. Plasmatic TNF-α level allows for the selection of patients who may benefit the most from this perioperative strategy.

Clinical trial identification

NCT03528785.

Editorial acknowledgement

Legal entity responsible for the study

D. Melisi.

Funding

Servier.

Disclosure

D. Melisi: Financial Interests, Personal, Advisory Board: Servier. All other authors have declared no conflicts of interest.