As reported in The Lancet by Zev A. Wainberg, MD, and colleagues, the phase III NAPOLI-3 trial has shown a modest but significant improvement in overall survival with first-line NALIRIFOX (liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil) vs nab-paclitaxel and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.
Zev A. Wainberg, MD
In the open-label trial, 770 patients from sites in 18 countries were randomly assigned between February 2020 and August 2021 to receive NALIRIFOX (n = 383) or nab-paclitaxel/gemcitabine (n = 387). NALIRIFOX was given as liposomal irinotecan at 50 mg/m², oxaliplatin at 60 mg/m², leucovorin at 400 mg/m², and fluorouracil at 2,400 mg/m² as a continuous infusion over 46 hours on days 1 and 15 of 28-day cycles; nab-paclitaxel/gemcitabine was given as nab-paclitaxel at 125 mg/m² and gemcitabine at 1,000 mg/m² on days 1, 8, and 15 of 28-day cycles. Treatment continued until radiographic disease progression or unacceptable toxicity. The primary endpoint was overall survival in the intention-to-treat population.
Median follow-up was 16.1 months (interquartile range = 13.4–19.1 months). Median overall survival was 11.1 months (95% confidence interval [CI] = 10.0–12.1 months) in the NALIRIFOX group vs 9.2 months (95% CI = 8.3–10.6 months) in the nab-paclitaxel/gemcitabine group (hazard ratio [HR] = 0.83, 95% CI = 0.70–0.99, P = .036). Rates at 12 and 18 months were 45.6% vs 39.5% and 26.2% vs 19.3%, respectively.
Median progression-free survival was 7.4 months (95% CI = 6.0–7.7 months) in the NALIRIFOX group vs 5.6 months (95% CI = 5.3–5.8 months) in the nab-paclitaxel/gemcitabine group (HR = 0.69, 95% CI = 0.58–0.83, P < .0001). Rates at 12 and 18 months were 27.4% vs 13.9% and 11.4% vs 3.6%, respectively. Subsequent systemic anticancer therapy was received by 51% of patients in the NALIRIFOX group and 54% of those in the nab-paclitaxel/gemcitabine group, most commonly gemcitabine-based treatment (41%) in the NALIRIFOX group and fluorouracil-based treatment (35%) in the nab-paclitaxel/gemcitabine group.
Grade ≥ 3 adverse events occurred in 87% of patients in the NALIRIFOX group and 86% of patients in the nab-paclitaxel/gemcitabine group. The most common grade 3 or 4 adverse events were diarrhea (20%), hypokalemia (15%), and neutropenia (14%) in the NALIRIFOX group, and neutropenia (25%) and anemia (17%) in the nab-paclitaxel/gemcitabine group. Serious adverse events occurred in 54% vs 52% of patients; adverse events led to discontinuation of treatment in 25% vs 23%. Death considered related to treatment occurred in six patients (2%) in the NALIRIFOX group and eight patients (2%) in the nab-paclitaxel/gemcitabine group.
The investigators concluded, “Our findings support use of the NALIRIFOX regimen as a possible reference regimen for first-line treatment of metastatic pancreatic ductal adenocarcinoma.”
Dr. Wainberg, of the David Geffen School of Medicine, University of California, Los Angeles, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Ipsen. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.