Zev A. Wainberg, MD, discusses the evaluation of liposomal irinotecan plus 5-fluorouracil leucovorin, and oxaliplatin vs nab-paclitaxel plus gemcitabine in the phase 3 NAPOLI 3 trial in patients with metastatic pancreatic ductal adenocarcinoma.
Zev A. Wainberg, MD, professor of medicine, University of California, Los Angeles (UCLA), co-director, the UCLA GI Oncology Program, discusses the evaluation of liposomal irinotecan (Onivyde) plus 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (NALIRIFOX) vs nab-paclitaxel (Abraxane) plus gemcitabine in the phase 3 NAPOLI 3 trial (NCT04083235) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Findings presented at the 2023 Gastrointestinal Cancers Symposium from the final efficacy analysis of the trial showed that liposomal irinotecan plus NALIRIFOX produced a clinically meaningful and statistically significant improvement in both overall survival (OS) and progression-free survival (PFS). At a median follow-up of 16.1 months (95% CI, 15.3-16.8), 383 patients treated with liposomal irinotecan plus NALIRIFOX experienced 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 387 patients given nab-paclitaxel plus gemcitabine (HR, 0.83; 95% CI, 0.70-0.99; P = .04).
Additionally, the median PFS for patients treated with liposomal irinotecan/NALIRIFOX was 7.4 months (95% CI, 6.0-7.7) vs 5.6 months (95% CI, 5.3-5.8) for those in the nab-paclitaxel/gemcitabine arm (HR, 0.69; 95% CI, 0.58-0.83; P< .0001).
Patients enrolled in NAPOLI 3 were randomly assigned 1:1 to 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 continued until disease progression, unacceptable toxicity, or study withdrawal.
OS served as the primary end point, and secondary end points included investigator-assessed PFS and overall response rate, as well as safety.
These findings could indicate that nab-paclitaxel plus gemcitabine is inferior to combination chemotherapy regimens in the frontline setting, and nab-paclitaxel plus gemcitabine may be considered as a second-line therapy, Wainberg says.
Notably, lower rates of grade 3/4 peripheral neuropathy were observed in patients treated with liposomal irinotecan plus NALIRIFOX (3.2%) vs nab-paclitaxel plus gemcitabine (5.8%). Investigators hoped to see this trend with the lower dose of oxaliplatin in the NALIRIFOX regimen, Wainberg concludes.