FDA Approves First-Line NALIRIFOX for Metastatic PDAC

The FDA has approved liposomal irinotecan (Onivyde), 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (NALIRIFOX) as a first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (PDAC).¹

Data from the phase 3 NAPOLI 3 trial (NCT04083235) serve as the basis for this approval, as patients with PDAC treated with NALIRIFOX had a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared with patients treated with nab-paclitaxel (Abraxane) in the study.²

At a median follow-up of 16.1 months (95% CI, 15.3-16.8), patients treated with NALIRIFOX (n = 383) had a median OS of 11.1 months (95% CI, 10.0-12.1) compared with 9.2 months (95% CI, 8.3-10.6) for those given nab-paclitaxel and gemcitabine (n = 387; HR, 0.83; 95% CI, 0.70-0.99; P = .04). In the NALIRIFOX arm, the median PFS was 7.4 months (95% CI, 6.0-7.7) vs 5.6 months (95% CI, 5.3-5.8) in the nab-paclitaxel/gemcitabine arm (HR, 0.69; 95% CI, 0.58-0.83; P < .0001).

Pancreatic cancer anatomy concept , malignant tumor of pancreas: © Лилия Захарчук - stock.adobe.com

NAPOLI 3 was an open-label, multicenter, phase 3 trial in which patients with confirmed metastatic PDAC were enrolled if they were previously untreated in the metastatic setting, and randomized in a 1:1 fashion where they received 50 mg/m² of liposomal irinotecan plus 2400 mg/m2 of 5-FU, 400 mg/m² of leucovorin, and 60 mg/m² of oxaliplatin on days 1 and 15 of each 28-day cycle, or 1000 mg/m² of gemcitabine plus 125 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or study withdrawal.³

Investigators assessed the primary end point of OS, along with secondary end points including PFS, overall response rate, and safety. Exploratory end points of health-related quality-of-life and biomarker assessments were also evaluated in the study.

A total of 770 patients were enrolled and assigned to receive NALIRIFOX (n = 383) or nab-paclitaxel-gemcitabine (n = 387). Patients given NALIRIFOX had an ORR of 41.8% (95% CI, 36.8%-46.9%), including a complete response (CR) rate of 0.3% in both arms, and a partial response (PR) rate of 41.5%, a stable disease (SD) rate of 25.8%, and a progressive disease (PD) rate of 9.9% in the liposomal irinotecan/NALIRIFOX arm.²

The ORR among the patients treated with nab-paclitaxel/gemcitabine was 36.2% (95% CI, 31.4%-41.2%). This included a PR rate of 35.9%, SD rate of 26.1%, and PD rate of 14.5%, respectively.

For safety, grade 3 or 4 treatment-emergent adverse events which were the most common among at least 10% of patients in the NALIRIFOX arm vs nab-paclitaxel/gemcitabine arm included diarrhea (20.3% v 4.5%), nausea (11.9% v 2.6%), hypokalemia (15.1% v 4.0%), anemia (10.5% v 17.4%) and neutropenia (14.1% v 24.5%).

REFERENCES:

1. FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. News release. FDA. February 13, 2024. Accessed February 13, 2024. http://tinyurl.com/2tkybz68

2. 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. J Clin Oncol. 2023;41(suppl 4):LBA661. doi:10.1200/JCO.2023.41.3_suppl.LBA661

3. A study to assess the effectiveness and safety of irinotecan liposome injection, 5-fluorouracil/leucovorin plus oxaliplatin in patients not previously treated for metastatic pancreatic cancer, compared to nab-paclitaxel+gemcitabine treatment (NAPOLI 3). ClinicalTrials.gov. Updated March 13, 2023. Accessed September 25, 2023. https://clinicaltrials.gov/ct2/show/NCT04083235