Dr Wainberg on the FDA Approval of NALIRIFOX in mPDAC

Zev A. Wainberg, MD, professor, medicine, University of California, Los Angeles (UCLA) codirector, UCLA Gastrointestinal Oncology Program, discusses the significance of the FDA approval of NALIRIFOX (irinotecan liposome injection [Onivyde], 5-fluorouracil, leucovorin, and oxaliplatin) for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

On February 13, 2024, the FDA approved NALIRIFOX for the treatment of patients with mPDAC. This regulatory decision was supported by findings from the phase 3 NAPOLI 3 trial (NCT04083235), results from which were published in The Lancet in October 2023.

NAPOLI 3 randomly assigned 770 patients with mPDAC in a 1:1 ratio to receive either NALIRIFOX (n = 383) or standard dosing of nab-paclitaxel (Abraxane) plus gemcitabine (n = 387) as first-line therapy. The primary end point of this trial was overall survival (OS) in the intention-to-treat population.

At a median follow-up of 16.1 months (IQR, 13.4-19.1), NALIRIFOX delivered a statistically significant OS benefit vs gemcitabine plus nab-paclitaxel, at 11.1 months (95% CI, 10.0-12.1) vs 9.2 months (95% CI, 8.3-10.6), respectively (HR, 0.83; 95% CI, 0.70-0.99; P = .036). The 12-month OS rates in the NALIRIFOX and gemcitabine/nab-paclitaxel arms were 45.6% (95% CI, 40.5%-50.5%) and 39.5% (95% CI, 34.6%-44.4%), respectively. The 18-month OS rates were 26.2% (95% CI, 20.9%-31.7%) and 19.3% (95% CI, 14.8%-24.2%), respectively.

Furthermore, the median progression-free survival (PFS) with NALIRIFOX was 7.4 months (95% CI, 6.0-7.7) vs 5.6 months (95% CI, 5.3-5.8) with gemcitabine/nab-paclitaxel (HR, 0.69; 95% CI, 0.58-0.83; P < .0001). The 12-month PFS rates in the NALIRIFOX and gemcitabine/nab-paclitaxel arms were 27.4% (95% CI, 22.3%-32.7%) and 13.9% (95% CI, 9.7%-18.9%), respectively. The 18-month PFS rates were 11.4% (95% CI, 7.1%-16.9%) and 3.6% (95% CI, 0.5%-12.3%), respectively.

NALIRIFOX elicited an overall response rate (ORR) of 41.8% (95% CI, 36.8%-46.9%) and a median duration of response (DOR) of 7.3 months (95% CI, 5.8-7.6). In the gemcitabine/nab-paclitaxel arm, these values were 36.2% (95% CI, 31.4%-41.2%) and 5.0 months (95% CI, 3.8-5.6), respectively. The OR for ORR was 1.26 (95% CI, 0.95-1.69; P = .11), and the HR for DOR was 0.67 (95% CI, 0.48-0.93).