FDA Approves First-Line NALIRIFOX for Metastatic PDAC
Liposomal irinotecan with 5-fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX) is now an FDA-approved treatment option for patients with metastatic pancreatic ductal adenocarcinoma.
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
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