Dr Pant on the Integration of NALIRIFOX Into the Frontline Metastatic Pancreatic Cancer Paradigm

"We have to watch out for diarrhea in our patients [treated with NALIRIFOX], which can be slightly increased. Otherwise, I believe [NALIRIFOX] is a very appropriate regimen for patients in the frontline setting.”

Shubham Pant, MD, MBBS, a professor in the Department of Gastrointestinal (GI) Medical Oncology and director of clinical research at the Sheikh Zayed Center For Pancreatic Cancer Research at The University of Texas MD Anderson Cancer Center, discussed the integration of NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil, and leucovorin) into the frontline treatment landscape for metastatic pancreatic cancer, as well as factors informing treatment selection in this setting.

NALIRIFOX was added to the frontline armamentarium following its FDA approval in February 2024, which was supported by data from the phase 3 NAPOLI 3 study (NCT04083235). In this trial, patients treated with NALIRIFOX (n = 383) achieved a statistically significant improvement in overall survival (OS) compared with those who received gemcitabine plus nab-paclitaxel (Abraxane; n = 387). The median OS was 11.1 months (95% CI, 10.0-12.1) with NALIRIFOX vs 9.2 months (95% CI, 8.3-10.6) for those receiving gemcitabine and nab-paclitaxel (HR, 0.84; 95% CI, 0.71-0.99; P = .0403). The regimen also produced a median progression-free survival of 7.4 months (95% CI, 6.0-7.7) vs 5.6 months (95% CI, 5.3-5.8) in the control arm (HR, 0.70; 95% CI, 0.59-0.85; P = 0.0001).

Beyond survival metrics, Pant highlighted the distinct safety profile of the regimen. He noted that NALIRIFOX is associated with a lower incidence of neuropathy, likely due to the lower 60-mg/m² dose of oxaliplatin that was used in the NAPOLI 3 protocol.

Pant emphasized the importance of remaining vigilant regarding GI toxicities, as diarrhea can be slightly increased with this regimen. For patients already experiencing gut intolerance or pre-existing diarrhea issues, alternative frontline options—such as FOLFIRINOX (fluorouracil, oxaliplatin, and irinotecan) or gemcitabine plus nab-paclitaxel—may be more appropriate. Patient performance status and patient comorbidities, such as diabetes-related neuropathy or other core issues such as nausea and vomiting, should be considered when selecting between these options, Pant added. Ultimately, Pant concluded that NALIRIFOX represents a highly effective and appropriate frontline option for the broader metastatic pancreatic cancer population.