Dr Spencer on First-Line Chemo Selection in Metastatic Pancreatic Adenocarcinoma

“Similar to FOLFIRINOX, NALIRIFOX does give us a certain degree of disease control, potentially even some management or shrinkage of disease, which is often critical for symptom relief.”

Kristen Spencer, DO, an associate professor in the Department of Medicine at NYU Grossman School of Medicine and director of the Phase 1 Developmental Therapeutics Program at Perlmutter Cancer Center, described first-line chemotherapy selection in metastatic pancreatic adenocarcinoma as a goal-directed process focused on achieving early disease control, improving symptom burden, and preserving tolerability over a clinically meaningful treatment duration.

In this context, Spencer noted that NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) can help meet core first-line objectives that clinicians often seek with FOLFIRINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin), namely rapid tumor control and the potential for objective shrinkage that may translate into symptom relief.

Spencer emphasized that a key practical differentiator between NALIRIFOX and traditional FOLFIRINOX is the oxaliplatin exposure. Because oxaliplatin is delivered at a lower dose in NALIRIFOX, Spencer highlighted the potential for reduced oxaliplatin-associated neurotoxicity. Peripheral neuropathy is a frequent, sometimes unpredictable, dose-limiting adverse effect that can emerge early and accumulate over time, she noted, adding that mitigating that risk may allow some patients to remain on an active multi-agent regimen longer, maintaining disease control while preserving functional status. From Spencer’s perspective, this tolerability consideration is directly aligned with first-line goals in the incurable, metastatic setting, where sustaining benefit with acceptable quality of life is often as important as achieving an initial response.

When guiding selection among NALIRIFOX, FOLFIRINOX, and gemcitabine plus nab-paclitaxel (Abraxane), Spencer framed decision-making around patient-specific factors that influence both feasibility and therapeutic intent. These include baseline performance status and frailty, symptom burden and urgency of response, pre-existing or high-risk neuropathy, hepatic function and biliary obstruction history, anticipated gastrointestinal toxicities, cytopenia risk, and the patient’s ability to adhere to infusion schedules and supportive care requirements.

In practice, Spencer conveyed that the choice is less about a single “best” regimen and more about matching regimen intensity and toxicity profile to the individual’s goals in order to maximize the likelihood of early control and treatment adherence.