Sequencing mPDAC Therapy Beyond First Line: Clinical and Patient-Centered Strategies

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The comparative toxicity profiles between NALIRIFOX and gemcitabine/nab-paclitaxel significantly influence treatment selection and patient counseling in metastatic pancreatic cancer. NALIRIFOX demonstrates superior neuropathy profiles due to reduced oxaliplatin dosing, lower neutropenia rates compared with gemcitabine/nab-paclitaxel, but increased gastrointestinal toxicity, particularly diarrhea. These 3 major toxicity differences guide personalized treatment selection based on patient-specific risk factors and quality of life priorities.

Thrombocytopenia represents an underappreciated but clinically significant toxicity associated with gemcitabine/nab-paclitaxel, often becoming dose-limiting due to limited treatment options for severe platelet reduction. This factor frequently influences treatment sustainability and requires careful monitoring throughout therapy. The balanced toxicity profile considerations must account for both acute treatment tolerability and long-term effects, particularly in patients anticipated to receive prolonged therapy for locally advanced or slowly progressive metastatic disease.

Dose-reduction strategies can make both NALIRIFOX and gemcitabine/nab-paclitaxel comparable in terms of tolerability, emphasizing the importance of flexible dosing approaches. Treatment selection ultimately depends on individual patient factors, baseline organ function, performance status, and personal preferences regarding specific adverse effect profiles. The goal remains maintaining patients on effective therapy for extended periods while preserving quality of life and functional independence throughout treatment.