Use of liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in neoadjuvant pancreatic adenocarcinoma: NEO-Nal-IRI trial.

BACKGROUND: While neoadjuvant FOLFIRINOX is an effective regimen for pancreatic ductal adenocarcinoma (PDAC), toxicity frequently limits its use. Nanoliposomal irinotecan (nal-IRI) offers improved pharmacokinetic properties and may mitigate some of the side effects. We conducted a multi-institutional, phase II study to evaluate the safety and clinical activity of neoadjuvant NALIRIFOX (nal-IRI, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with resectable and borderline resectable (R/BR) PDAC. METHODS: Patients with untreated R/BR PDAC received eight cycles of neoadjuvant NALIRIFOX. The primary endpoint was the 30-day post-operative major complication rate among resected patients. Secondary endpoints included treatment completion rate, R0 resection rate, objective response rate (ORR), biochemical (CA19-9) and radiographic responses, nodal downstaging, and quality of life (QoL by FACT-G). RESULTS: Of the 45 enrolled patients, 73% completed all eight cycles of neoadjuvant NALIRIFOX. 34 patients (76%) underwent attempted surgery, of whom 29 (64%) had complete resection (15 BR patients and 14 R patients). The 30-day post-operative major complication rate was 10% (95% CI, 2.2-27%, p = 0.012), meeting the pre-specified threshold. R0 resection was achieved in 90% of resected patients. The radiographic ORR was 45% (95% CI, 29-62%), and the clinical benefit rate was 73% (95% CI, 58-85%). CONCLUSION: Neoadjuvant NALIRIFOX is a safe and active regimen in R/BR PDAC with a low post-operative complication rate, high treatment completion and R0 resection rates, and meaningful clinical responses. These findings support further investigation of NALIRIFOX as part of a total neoadjuvant therapy (TNT) approach in PDAC. ClinicalTrials.gov identifier: NCT03483038.