NALIRIFOX Dose Reductions Linked to Improved Survival in Pancreatic cancer, New Analysis Shows
New data presented at a recent medical meeting suggests that dose reductions of NALIRIFOX – a chemotherapy regimen for metastatic pancreatic ductal adenocarcinoma (mPDAC) – do not diminish efficacy and may even improve overall survival (OS) compared to maintaining the initial dose. The findings, a post-hoc analysis of the pivotal NAPOLI 3 trial, offer a potentially reassuring approach for clinicians treating patients with this aggressive cancer, where treatment options are limited.
Pancreatic cancer is notoriously difficult to treat, and dose reductions are often a necessary reality due to treatment-related toxicities.Historically, clinicians have been hesitant to reduce doses of chemotherapy for pancreatic cancer, fearing it would compromise the treatment’s effectiveness, as patients frequently enough have few alternative options. Though,this analysis challenges that assumption,demonstrating that dose adjustments with NALIRIFOX might potentially be a beneficial strategy.
the analysis of the NAPOLI 3 trial revealed that patients experiencing dose reductions in either the irinotecan or oxaliplatin components of NALIRIFOX actually demonstrated improved median OS.Specifically, patients with liposomal irinotecan dose reductions achieved a median OS of 12.6 months, compared to 9.4 months for those who did not have a dose reduction.Similarly, patients with oxaliplatin dose reductions had a median OS of 13.5 months versus 7.7 months for those without dose reductions.
Further analysis indicated that the greatest benefit was observed with the second-to-last dose reduction. Starting at 50 mg/m2 of irinotecan, median OS was 9.1 months. Reducing to 32.5 mg/m2 yielded a median OS of 16.9 months, and even the lowest dose of 25 mg/m2 resulted in a median OS of 13.5 months – still exceeding the survival seen with the starting dose. A similar trend was observed with oxaliplatin, with the second-to-last dose demonstrating the best outcome at 17.1 months.
researchers emphasize that these findings are from subgroup analyses and should be interpreted with caution. However, the data suggests that dose delays coupled with dose reductions are preferable to simply delaying and restarting at the original dose. The NAPOLI 3 trial, published in the Lancet in 2023, originally demonstrated the superiority of NALIRIFOX over nab-paclitaxel and gemcitabine in treatment-naive patients with mPDAC.1 This latest analysis, presented at a recent meeting and detailed in the Journal of Clinical Oncology (2025;43(suppl 4):716),3 provides valuable insight into optimizing NALIRIFOX treatment in clinical practise.
References:
- Wainberg ZA,melisi D,Macarulla T,et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised,open-label,phase 3 trial. Lancet. 2023;402(10409):1272-1281. doi:10.1016/S0140-6736(23)01366-1
- Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.doi:10.1056/NEJMoa1011923
- Patel AJ, Laursen AA, Cockrum P, et al.Effect of dose adjustments on overall survival (OS) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with NALIRIFOX: A post hoc analysis of NAPOLI 3. J clin Oncol. 2025;43(suppl 4):716. doi:10.1200/JCO.2025.43.4_suppl.716
