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
Study Details
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.
Overall Survival
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.
KEY POINTS
- NALIRIFOX significantly improved overall survival vs nab-paclitaxel/gemcitabine.
- Median overall survival was 11.1 vs 9.2 months, with rates at 12 and 18 months of 45.6% vs 39.5% and 26.2% vs 19.3%.
Adverse Events
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.
