Dr Wainberg on Selecting Between FOLFIRINOX and NALIRIFOX in Frontline Pancreatic Cancer

"NALIRIFOX has lower doses of oxaliplatin than FOLFIRINOX, and thus [is associated with] a lower rate of peripheral neuropathy. It also theoretically has some advantages in patients with UGT1A1 polymorphisms. By and large, it's a similar calculation and a similar discussion for both of these [regimens, however].”

Zev A. Wainberg, MD, MSc, a professor of medicine in the Department of Medicine at the University of California, Los Angeles (UCLA), and co-director of the UCLA GI Oncology Program, discussed factors informing treatment selection between NALIRIFOX (liposomal irinotecan (Onivyde), oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) and FOLFIRINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin) as frontline chemotherapy for patients with metastatic pancreatic cancer, in the absence of direct comparisons between these 2 regimens.

Wainberg emphasized that comparisons of NALIRIFOX and FOLDIRINOX are currently based only on cross-trial data. The overall efficacy and toxicity profiles of these 2 regimens do not appear significantly different when performing cross-trial comparisons, he reported. However, he explained that NALIRIFOX uses lower doses of oxaliplatin compared with FOLFIRINOX, resulting in a potentially lower rate of peripheral neuropathy.

Moreover, NALIRIFOX may hold theoretical advantages for specific patient groups, such as patients with UGT1A1 polymorphisms, as patients with this mutation may be less likely to be adversely affected by this regimen.

However, data from an analysis of the effect of UGT1A1*28 polymorphisms on the tolerability of NALIRIFOX in the phase 3 NAPOLI-3 trial (NCT04083235), which were presented at the 2025 ASCO Gastrointestinal Cancers Symposium, showed a similar incidence of treatment-emergent adverse effects in patients with homozygous vs non-homozygous UGT1A1*28 status, suggesting that this status did not substantially influence the safety profile or subsequent need for dose reductions of liposomal irinotecan.

Although these theoretical advantages exist, Wainberg concluded that the overall clinical calculation and discussion surrounding both regimens are similar. He instead prefers to focus on available clinical trial data rather than relying too heavily on cross-trial comparisons.