(mPDAC) in a global phase 3 trial dubbed NAPOLI-3.
Liposomal irinotecan (Onivyde) plus 5-fluorouracil/leucovorin and oxaliplatin (together known as NALIRIFOX) extended both overall and progression-free survival compared with gemcitabine plus nab-paclitaxel when used as first-line therapy in treatment-naive patients with mPDAC.
“These results support the NALIRIFOX regimen as a new regimen for the first-line treatment of patients with metastatic PDAC,” said lead study author Zev A. Wainberg, MD, professor of medicine at University of California, Los Angeles (UCLA) and codirector of the UCLA GI Oncology Program. “This study indicates that the more aggressive chemotherapy approach should be considered for those patients who are able to tolerate it.”
The findings were presented at the ASCO Gastrointestinal Cancers Symposium 2023.
Liposomal irinotecan administered with 5-fluorouracil/leucovorin has been approved in both the United States and Europe for patients with mPDAC who experience disease progression after treatment with gemcitabine-based therapy. This new trial investigated the approach as a first-line option.
It involved 770 patients who were randomly assigned to one of two treatment arms: NALIRIFOX (liposomal irinotecan 50 mg/m2, 5-fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, and oxaliplatin 60 mg/m2; days 1 and 15 of 28-day cycle) or gemcitabine 1,000 mg/m2 plus nab-paclitaxel 125 mg/m2 (days 1, 8, and 15 of 28-day cycle).
Most patients in both study arms were male (53.3% and 59.4% for liposomal irinotecan/NALIRIFOX recipient vs. the control group, respectively), had at least three metastatic sites (38.9% and 36.4%), had liver metastases (80.2% and 80.4%), and had their main tumor located outside the head of the pancreas (61.6% and 59.7%).
Most patients (65% in both arms) were treated outside of North America and East Asia.
“This is truly a global study, enrolling in over 20 countries, with a mix of both academic and community centers,” said Dr. Wainberg.
At a median follow-up of 16.1 months, 544 events had occurred.
“The study met its primary endpoint of overall survival by improving the median from 9.2 months with gemcitabine plus nab-paclitaxel to 11.1 months with NALIFIROX-treated group,” said Dr. Wainberg. “The hazard ratio was 0.84, with a P value of .04.”
Significant improvement was also observed in progression-free survival: 7.4 months for NALIFIROX vs. 5.6 months for gemcitabine plus nab-paclitaxel (hazard ratio, 0.69; P < .0001).
The overall response rate for liposomal irinotecan/NALIRIFOX vs. nab-paclitaxel/gemcitabine was 41.8% vs. 36.2%, and the complete response rate was 0.3% in both arms.
Dr. Wainberg noted that about half of the patients in both groups underwent subsequent anticancer therapy (50.5% vs. 54.4%); this included systemic treatments, surgery, and radiation therapy.
Grade 3/4 treatment-emergent adverse events reported in ≥ 10% of patients in both groups included diarrhea (20.3% vs. 4.5%), nausea (11.9% vs. 2.6%), hypokalemia (15.1% vs. 4.0%), anemia (10.5% vs. 17.4%), and neutropenia (14.1% vs. 24.5%).
“When one looks at the nuances in the patients and the toxicity profiles, we can see these two regimens have very different toxicity profiles,” Dr. Wainberg said. “There was also less peripheral neuropathy seen in the NALIRIFOX arm relative to the nab-paclitaxel/gemcitabine arm.”
The differences in the toxicity profiles were related to the mechanisms of action, Dr. Wainberg explained. “No new safety concerns with the NALIRIFOX regimen were identified.”