Combination treatment with liposomal irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX) outperformed treatment with nab-paclitaxel and gemcitabine (Gem-NabP) in patients with metastatic pancreatic ductal adenocarcinoma in the NAPOLI-3 trial.

NALIRIFOX improved both progression-free survival (PFS) and overall survival (OS), compared with Gem-NabP, for patients who had no prior treatment in the metastatic setting.

These results were presented at the 2023 ASCO Gastrointestinal Cancers Symposium by Zev A. Wainberg, MD, of UCLA Santa Monica Medical Center.

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The phase 3 NAPOLI-3 trial ( Identifier: NCT04083235) included 770 patients with pancreatic ductal adenocarcinoma not previously treated in the metastatic setting. Patients were randomly assigned to receive NALIRIFOX (n=383) or Gem-NabP (n=387) until disease progression or toxicity.

The median age was 64 years in the NALIRIFOX arm and 65 years in the Gem-NabP arm. More than half of patients were men (53.3% and 59.4%, respectively), most were White (82.2% and 83.7%), and most had liver metastasis (80.2% and 80.4%).

The objective response rate was higher in the NALIRIFOX arm than in the Gem-NabP arm (41.8% and 36.2%, respectively). The complete response rate was 0.3% in both arms.

About half of patients in each arm received subsequent anticancer therapy (50.5% in the NALIRIFOX arm and 54.4% in the Gem-NabP arm).

Patients in the NALIRIFOX arm had significantly longer PFS and OS. The median OS was 11.1 months in the NALIRIFOX arm and 9.2 months in the Gem-NabP arm (hazard ratio [HR], 0.83; 95% CI, 0.70-0.99; P =.04). The median PFS was 7.4 months and 5.6 months, respectively (HR, 0.69; 95% CI, 0.58-0.83; P <.0001).

In subgroup analyses, NALIRIFOX was generally favored over Gem-NabP for both survival outcomes. PFS was significantly better with NALIRIFOX across all subgroups except among patients with 2 metastatic sites or with an ECOG performance status of 1.

The rate of treatment-related adverse events (TRAEs) was 95.1% in the NALIRIFOX arm and 92.9% in the Gem-NabP arm. The rate of grade 3 or higher TRAEs was 70.8% and 68.1%, respectively. The rate of fatal TRAEs was 1.6% and 2.1%, respectively.

The 2 regimens had different safety profiles, with NALIRIFOX recipients generally experiencing more non-hematologic toxicities (eg, diarrhea, nausea, vomiting, and hypokalemia) and Gem-NabP recipients reporting more hematologic toxicities (eg, neutropenia, anemia, and thrombocytopenia).

“These results support the NALIRIFOX regimen as a new reference regimen for the first-line treatment of patients with metastatic pancreatic cancer and hopefully something we can build off of in the future,” Dr Wainberg concluded.

Disclosures: This research was supported by Ipsen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


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. ASCO GI 2023. January 19-21, 2023. Abstract LBA661.