Real-world data confirm NALIRIFOX efficacy and manageable toxicity in metastatic pancreatic cancer

A multicenter Austrian study published in ESMO Open (2025) assessed the real-world performance of NALIRIFOX—a triplet chemotherapy combining nanoliposomal irinotecan, 5-fluorouracil/leucovorin, and oxaliplatin—in 80 patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The findings confirm that NALIRIFOX retains strong clinical efficacy and a favorable safety profile outside clinical trial settings.

After a median follow-up of 13.7 months, the median time to failure of strategy (TFS) was 5.66 months, and overall survival (OS) reached 11.15 months, closely mirroring outcomes from the phase III NAPOLI 3 trial. Patients who met NAPOLI 3 inclusion criteria achieved even better results (OS 12.9 months; TFS 6.1 months). The disease control rate (DCR) was 57.5%, including a 37.5% partial response rate.

Toxicities were generally manageable, with grade 3–4 adverse events in 22.5% of patients—lower than reported in controlled studies. Fatigue (55%), diarrhea (50%), and peripheral neuropathy (48%) were the most common side effects. No treatment-related deaths occurred.

Molecular analyses revealed that 20% of patients harbored homologous recombination repair mutations (HRRm)—mainly in BRCA1/2, ARID1A, and ATM. This subgroup achieved significantly longer survival (OS 16.2 vs 11.1 months; HR 0.34; p=0.043) and improved disease control (100% vs 52%). Conversely, KRAS G12D/V mutations were associated with poorer OS (11.1 months vs not reached; p<0.05), reinforcing their negative prognostic role even under triplet chemotherapy.

The authors conclude that NALIRIFOX offers durable benefit with lower toxicity in clinical practice, especially in genomically selected populations. These results validate the NAPOLI 3 trial findings and support integrating molecular profiling—particularly HRR and KRAS status—into treatment decisions for metastatic pancreatic cancer.

#PancreaticCancer #NALIRIFOX #HRRMutations #KRAS #RealWorldEvidence

Editorial Note

This text was organized with the support of artificial intelligence, but it was critically reviewed and validated by a qualified professional to ensure scientific accuracy and reliability.