Evaluating the Impact Of UGT1A1*28 Status On Tolerability Of NALIRIFOX In mPDAC
Panelists discuss how UGT1A1 mutations may predict increased diarrhea risk in patients receiving NALIRIFOX, with genetic testing potentially valuable for identifying patients who need more aggressive supportive care or dose modifications, particularly those with borderline performance status.
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EP: 2.Insights From The NAPOLI-3 and PRODIGE4 Trials In Metastatic Pancreatic Adenocarcinoma
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Dr. Shah discusses a poster presented at ASCO GI by Dr. Min Abdel Rahim examining the role of UGT1A1 mutations in patients treated with NALIRIFOX in the NAPOLI-3 trial. This analysis is particularly relevant given the higher risk of diarrhea associated with NALIRIFOX, requiring proactive management strategies for optimal patient outcomes.
The study investigated whether UGT1A128 homozygosity is linked to increased diarrhea risk in patients receiving irinotecan-based therapy. Findings confirmed that this genetic variation is associated with reduced SN-38 (the active metabolite of irinotecan) clearance and increased toxicity. In the NAPOLI-3 trial, treatment-related adverse events, especially diarrhea, were more frequent in patients with UGT1A128 homozygosity.
This research highlights the potential value of genetic testing before initiating irinotecan-based therapies, particularly in patients with borderline performance status. While Dr. Shah acknowledges that such genotyping is not routinely performed in clinical practice, he suggests considering this approach for patients at higher risk of gastrointestinal intolerance or diarrhea. This personalized approach could help optimize treatment selection and improve outcomes by identifying patients who may require more aggressive supportive care or dose modifications.
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