Treatment Decision and Conclusion

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Based on comprehensive review of clinical evidence, mechanism of action, and level 1 data supporting NALIRIFOX, this regimen represents an excellent treatment option for the presented patient with locally advanced pancreatic adenocarcinoma. The patient’s excellent performance status, successful biliary decompression, and normalized bilirubin make him an ideal candidate for this intensive triplet regimen. NALIRIFOX offers the potential to maximize overall survival outcomes compared with standard doublet chemotherapy regimens.

Successful NALIRIFOX implementation requires meticulous attention to toxicity management and proactive adverse event prevention. Close monitoring for cytopenia with aggressive growth factor support, comprehensive diarrhea management protocols, and patient education regarding symptom recognition and management are essential components of care. The post hoc analyses from the NAPOLI-3 trial (NCT04083235) provide reassurance that appropriate dose modifications for toxicity management do not compromise survival outcomes, allowing clinicians to maintain treatment safety while preserving efficacy.

The evolving treatment landscape for pancreatic adenocarcinoma, from the ACCORD 11 and MPACT trials through the NAPOLI-1 (NCT01494506) and NAPOLI-3 trials, demonstrates continued progress in improving outcomes for this challenging malignancy. NALIRIFOX represents the latest advancement in first-line therapy, offering superior survival outcomes compared with gemcitabine plus nab-paclitaxel. For appropriately selected patients with excellent performance status and proper supportive care infrastructure, NALIRIFOX should be strongly considered as a preferred first-line treatment option to optimize survival outcomes in locally advanced and metastatic pancreatic adenocarcinoma.