Insights from ASCO 2025: What’s Next for Pancreatic Cancer? - Episode 8
Panelists discuss how real-world data suggest similar efficacy between NALIRIFOX and FOLFIRINOX, and how sequential therapy approaches using doublets don’t appear superior to up-front triplet regimens for appropriate patients.
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Real-world data comparing FOLFIRINOX and NALIRIFOX provide valuable insights but require cautious interpretation due to the inherent limitations of nonrandomized comparisons. Cross-trial analyses suggest numerical benefits favoring NALIRIFOX, but with identical median overall survival of 11.1 months, definitive conclusions remain elusive without direct randomized comparison. The IPHONE-MAX-PRO-61 trial investigated sequential therapy approaches using FOLFIRINOX plus NALIRIFOX or gemcitabine/nab-paclitaxel, but results didn’t demonstrate superiority over standard triplet regimens for first-line treatment.
The sequential therapy concept, while theoretically appealing for reducing toxicity, failed to show statistical significance between treatment arms in the 3-arm study design. Neither the individual doublet regimens nor the sequential approach provided compelling evidence to replace established triplet therapy in appropriately selected patients. For patients unable to tolerate triplet regimens, the primary limiting factor is often reluctance to accept port placement and continuous infusion pumps rather than concerns about 3-drug toxicity profiles.
Patient selection for doublet vs triplet therapy frequently centers on practical considerations, with some patients refusing central venous access for continuous infusion therapy. In such cases, gemcitabine/nab-paclitaxel becomes the preferred alternative, though oncologists typically encourage triplet therapy when medically appropriate. Even elderly patients older than 80 years can successfully receive modified triplet regimens, emphasizing the importance of individualized treatment decisions based on functional status rather than chronological age alone.