According to a post hoc analysis of the phase 3 NAPOLI trial, dose reductions of liposomal irinotecan or oxaliplatin did not adversely affect the overall survival (OS) among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who received NALIRIFOX.

These results were first presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.

In this open-label phase 3 trial, 770 patients with metastatic PDAC were randomized on a 1-to-1 basis to receive either NALIRIFOX (liposomal irinotecan in combination with 5-fluorouracil/leucovorin plus oxaliplatin) or gemcitabine plus nab-paclitaxel. NAPOLI met its primary end point, with NALIRIFOX significantly improving overall survival and progression free survival (PFS). This post hoc analysis explores the impact of liposomal irinotecan and oxaliplatin dose reductions on OS within the trial.

In the NAPOLI 3 trial, treatment-emergent adverse events resulted in a dose reduction for 198 patients who received NALIRIFOX and 184 who received gemcitabine plus nab-paclitaxel. In the safety population of the NALIRIFOX arm (n = 370) there were 194 patients who had a dose reduction of liposomal irinotecan, and 217 who had a dose reduction of oxaliplatin. Overall, the OS was longer among patients who did receive a dose reduction of either compared with those without a dose reduction. Additionally, patients who had a dose reduction experienced a longer duration of exposure and a higher cumulative dose. Study authors noted that the longer OS “may be related to longer time on therapy and an increased likelihood of dose adjustment.” The median OS of those patients who experienced a dose reduction of liposomal irinotecan was 12.6 months, and of those who experienced a dose reduction of oxaliplatin was 13.5 months. The median OS of those patients who did not receive dose reductions were 9.4 months (n = 176) and 7.7 months (n = 153), respectively.

Study authors concluded, “these data suggest a path forward to further optimize the OS of patients with [metastatic] PDAC receiving NALIRIFOX.”

Source:

Patel A, Laursen A, Cockrum P, et al. Effect of dose adjustments on overall survival in patients with metastatic pancreatic ductal adenocarcinoma treated with NALIRIFOX: a post hoc analysis of NAPOLI 3. Presented at ASCO Gastrointestinal Cancers Symposium; January 23-25, 2025. San Francisco, CA. Abstract 716