ASCO 2025: Insights on NALIRIFOX Use in Metastatic Pancreatic Ductal Adenocarcinoma From the NAPOLI-3 Trial

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Vincent Chung, MD, a medical oncologist at City of Hope, presented new insights from the NAPOLI-3 trial (NCT04083235), a pivotal phase 3 study evaluating NALIRIFOX (liposomal irinotecan [Onivyde; Ipsen Biopharmaceuticals] 50 mg/m², oxaliplatin 60 mg/m², leucovorin 400 mg/m², and fluorouracil 2400 mg/m², administered sequentially as a continuous intravenous infusion over 46 h) as a first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Previously published in The Lancet, results from NAPOLI-3 demonstrated a significant overall survival (OS) benefit of NALIRIFOX over the gemcitabine plus nab-paclitaxel regimen, solidifying its role as a guideline-supported option in frontline therapy.

In this interview with Pharmacy Times®, Chung discusses the clinical relevance of long-term survivors identified in the trial, practical considerations for managing adverse events (AEs), and how pharmacists can optimize dosing and supportive care to improve treatment tolerability and outcomes.

Pharmacy Times: Could you elaborate on the clinical significance of the NAPOLI-3 trial OS benefit and how it might influence first-line treatment decisions for mPDAC?

Vincent Chung, MD, is a medical oncologist at City of Hope, a national cancer research and treatment organization.

Vincent Chung, MD: NAPOLI-3 was an international phase 3 clinical trial conducted in 18 countries with 770 subjects accrued. NAPOLI-3 results showed superiority of NALIRIFOX over gemcitabine and nab-paclitaxel. Based upon this trial, NALIRIFOX is considered one of the recommended treatment regimens for first-line treatment of patients with metastatic disease. At the 2025 ASCO Annual Meeting, we reported baseline and demographic data of the 15 long-term survivors treated with the NALIRIFOX regimen in North America.

Pharmacy Times: How do the results for the secondary end points of the NAPOLI-3 trial support the use of NALIRIFOX in clinical practice?

Chung: A majority of the patients had over 3 metastases, which is a poor prognostic indicator, but otherwise had favorable characteristics such as Eastern Cooperative Oncology Group 0 and low carbohydrate antigen 19-9. Most patients in this long-term survivor group had dose reductions and dose delays, suggesting that aggressive management of toxicities potentially allows patients to remain on treatment longer to derive more benefit.

Pharmacy Times: What strategies do you recommend for pharmacists to manage grade 3 to 4 AEs from NALIRIFOX effectively?

Chung: The most common grade 3 to 4 AEs were neutropenia, diarrhea, and hypokalemia with NALIRIFOX treatment. Growth factor support helps prevent complications. Repetition of education on the management of toxicities effectively increases early intervention.

Pharmacy Times: A post-hoc analysis of the NAPOLI-3 trial indicated that dose reductions of liposomal irinotecan and oxaliplatin did not compromise OS. Can you discuss how this finding might inform dose adjustment protocols in pharmacy practice?

Chung: Adjustment of dose is individualized based upon baseline patient characteristics and toxicities. Early intervention potentially allows patients to stay on treatment longer, thus impacting OS.

Pharmacy Times: Given that both NALIRIFOX and FOLFIRINOX (folinic acid, fluorouracil, irinotecan hydrochloride [Camptosar; Pfizer], and oxaliplatin) are triplet regimens, how does NALIRIFOX compare in terms of efficacy and tolerability, and what factors should pharmacists consider when selecting between these options?

A microscopic photo of pancreatic adenocarcinoma cells with irregular ducts and dense fibrotic tissue.

Chung: There is no head-to-head comparison of NALIRIFOX vs FOLFIRINOX and cross-trial comparison is limited due to differences in eligibility criteria, patient characteristics, and dose modifications. Most oncologists utilize a dose reduced, modified FOLFIRINOX regimen, which will impact efficacy. In the PRODIGE trial [NCT01804790], FOLFIRINOX chemotherapy had grade 3 to 4 neutropenia, diarrhea, and neuropathy in 45.7%, 12.7%, and 9% of patients, respectively. For NALIRIFOX in the NAPOLI-3 trial, the percentages were 14%, 20%, and 3% respectively. Early judicious use of antidiarrheals is important.

Pharmacy Times: Were there any specific characteristics identified among long-term survivors in the NALIRIFOX arm that could guide patient selection or counseling?

Chung: This was a descriptive analysis so no direct conclusions can be made. Many patients with late-stage disease are symptomatic with weight loss, malnutrition and pain. Aggressive management may help with chemotherapy tolerance. This would be similar to prehabilitation for surgical patients to minimize complications.

Pharmacy Times: What supportive care measures, such as antiemetics or antidiarrheals, should pharmacists anticipate and prepare for when managing patients on NALIRIFOX?

Chung: Scheduled antiemetics with serotonin receptor antagonists and steroids for 3 days after chemotherapy can mitigate the nausea, fatigue, and anorexia. However, patients with diabetes will require close monitoring of blood sugars and adjustment of medications. Education on the early use of antidiarrheals is important. Commonly, patients will wait until they have multiple episodes over days before initiating therapy, which makes it more challenging to get control of symptoms.