First-line NALIRIFOX superior to standard treatment in mPDAC

The phase 3 NAPOLI-3 trial showed that liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin (NALIRIFOX) outperformed nab-paclitaxel plus gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma (mPDAC).

The phase 3 NAPOLI-3 trial (NCT04083235) compared nab-paclitaxel plus gemcitabine with NALIRIFOX for the first-line treatment of 770 patients with mPDAC [1]. Eligible patients were randomised 1:1 to evaluate the primary endpoint of overall survival (OS). Prof. Zev Wainberg (University of California Los Angeles, CA, USA) presented the late-breaking results.

After a median follow-up of 16.1 months, the OS was significantly improved in the NALIRIFOX arm compared with the control arm (median OS 11.1 months vs 9.2 months; HR 0.83; 95% CI 10.0–12.1; P=0.04, see Figure). Prof. Wainberg added that the OS curves started to separate from 3 months and remained separated through the further course of the study. Similarly, progression-free survival (PFS) was improved in patients receiving NALIRIFOX arm compared with those receiving nab-paclitaxel plus gemcitabine (median PFS 7.4 months vs 5.6 months; HR 0.69; 95% CI 0.58–0.83; P<0.0001). Additionally, all subgroups showed to have a benefit.

Figure: Overall survival of NALIRIFOX versus nab-paclitaxel plus gemcitabine [1]



NALIRIFOX, liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin; Gem, gemcitabine; NabP, nab-paclitaxel.

Prof. Wainberg mentioned that NALIRIFOX had a manageable safety profile, consistent with the toxicity profiles of the individual treatment components. Comparable rates of grade 3 or higher adverse events (AEs) were reported for the 2 study groups (87.0% and 86.0%). However, grade 3 or 4 haematologic AEs were more common among patients receiving nab-paclitaxel plus gemcitabine, whereas those who were exposed to NALIRIFOX showed higher rates of grade 3 or 4 diarrhoea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), and vomiting (7.0% vs 2.1%).

Prof. Wainberg concluded that these results support the administration of NALIRIFOX as first-line therapy for patients with mPDAC. Of note, NALIRIFOX is a new standard-of-care for fit patient if liposomal irinotecan is available in the first line.

1. Wainberg ZA, 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 (mPDAC). Late-breaking abstract 661, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.

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Posted on 17 March 202317 May 2024