NALIRIFOX Demonstrates Consistent Safety in Metastatic Pancreatic Cancer

The safety profile of first-line liposomal irinotecan (Onivyde) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX) in patients with metastatic pancreatic ductal adenocarcinoma was consistent with those previously reported findings, according to Zev A. Wainberg, MD, regarding the phase 3 NAPOLI-3 study (NCT04083235).

In an interview with CancerNetwork^®, lead author Wainberg, a professor of medicine at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gastrointestinal Oncology Program, discussed the safety of NALIRIFOX compared with gemcitabine plus nab-paclitaxel from the NAPOLI-3 study, which was presented at the 2023 Gastrointestinal Cancers Symposium.

In NAPOLI-3, common grade 3/4 treatment-emergent adverse effects observed in patients receiving NALIRIFOX vs those receiving gemcitabine plus nab-paclitaxel, respectively, included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%), and neutropenia (14.1% vs 24.5%).

Wainberg also discussed the trial’s limitations, which included the fact that it was not placebo controlled.

Transcript:

Most of the safety data are consistent with what we knew of these regimens. The NALIRIFOX had more GI toxicity than gemcitabine/nab-paclitaxel, and the gemcitabine/nab-paclitaxel had more cytopenias than NALIRIFOX. However, we were pleasantly pleased by a low rate of peripheral neuropathy in our study which, in the NALIRIFOX arm, indicated a lower dose of the cumulative oxaliplatin usage and that had important implications. Those were some of the main safety findings in the NAPOLI-3 trial.

There are always limitations to a study. It wasn’t placebo-controlled. There are certainly biases about which patients [should br included.] But this study took a really bread and butter group of patients, which is newly diagnosed metastatic pancreatic cancer, in centers all around the world, not in academic centers and community centers. There was not a huge number of differences in this kind of study than what we would expect in the real world.

Reference

Wainberg ZA, Melisi D, Macarulla T, et al. NAPOLI-3: A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). J Clin Oncol. 2023;41(suppl 4):LBA661. doi:10.1200/JCO.2023.41.3_suppl.LBA661