Dr Malalur on the Implications of NALIRIFOX in Pancreatic Ductal Adenocarcinoma

Pannaga G. Malalur, MBBS, medical oncology specialist, Gastrointestinal Cancers, The Ohio State University Comprehensive Cancer Center (OSUCCC) - James Cancer Hospital & Solove Research Institute, discusses the implications of the findings for the use of liposomal irinotecan (Onivyde) plus 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (NALIRIFOX) in the frontline setting for patients with metastatic pancreatic ductal adenocarcinoma (PDAC)

The phase 3 NAPOLI 3 trial (NCT04083235) evaluated the NALIRIFOX regimen nab-paclitaxel (Abraxane) plus gemcitabine in this patient population. Findings presented at the 2023 Genitourinary Cancers Symposium showed a clinically meaningful and statistically significant improvement in both overall survival (OS) and progression-free survival (PFS) with NALIRIFOX. At a median follow-up of 16.1 months (95% CI, 15.3-16.8), a median OS of 11.1 months (95% CI, 10.0-12.1) was observed in the 383 patients treated with NALIRIFOX vs 9.2 months (95% CI, 8.3-10.6) for the 387 patients treated with nab-paclitaxel plus gemcitabine (HR, 0.83; 95% CI, 0.70-0.99; P = .04).

The median PFS was 7.4 months (95% CI, 6.0-7.7) and 5.6 months (95% CI, 5.3-5.8) for those treated with NALIRIFOX and nab-paclitaxel/gemcitabine, respectively (HR, 0.69; 95% CI, 0.58-0.83; P < .0001).

Although safety data from the study demonstrated similar rates of grade 3 or higher treatment-emergent adverse effects (TEAEs) between the NALIRIFOX arm (87%) and the nab-paclitaxel/gemcitabine arm (86%), the AEs observed with NALIRIFOX varied from what was seen with standard of care chemotherapy, Malalur says. For example, patients treated with NALIRIFOX experienced a higher rates of gastrointestinal TEAEs, including nausea, vomiting, and diarrhea, and those treated with nab-paclitaxel plus gemcitabine experienced more cytopenias, Malalur explains.

The efficacy and safety data point to NALIRIFOX as a potential new first-line treatment option for patients with metastatic PDAC, and the varying TEAEs associated with the regimen and nab-paclitaxel/gemcitabine could allow for different choices for patients in this setting, Malalur concludes.