ArticleBMJ oncology2026
Real-world effectiveness of NALIRIFOX versus modified FOLFIRINOX or gemcitabine and nab-paclitaxel in first-line advanced pancreatic adenocarcinoma: a multicentre propensity-matched study.
Article in BMJ oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: To compare the real-world effectiveness and recorded safety of first-line liposomal irinotecan+oxaliplatin+fluorouracil+leucovorin (NALIRIFOX), modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (Gem/NabP) in treatment-naïve patients with advanced pancreatic ductal adenocarcinoma (PDAC) in Thailand. Methods and analysis: This retrospective, multicentre cohort study included adult patients with unresectable locally advanced or metastatic PDAC who initiated first-line NALIRIFOX, mFOLFIRINOX or Gem/NabP across 10 major Thai cancer centres between January 2021 and July 2024. Propensity score matching was performed to reduce treatment selection bias using age, sex, Eastern Cooperative Oncology Group performance status, metastatic burden, primary tumour location and baseline albumin. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Secondary outcomes were objective response rate (ORR) and grade ≥3 treatment-related adverse events. Safety analyses were limited to matched patients with sufficient follow-up documentation to assess toxicity retrospectively. Results: Of 513 eligible patients, 199 were included in the matched cohort: 52 received NALIRIFOX, 105 mFOLFIRINOX and 42 Gem/NabP. Median OS was 10.4 months for NALIRIFOX, 9.6 months for mFOLFIRINOX and 6.0 months for Gem/NabP. NALIRIFOX was associated with similar OS to mFOLFIRINOX (HR 1.09, 95% CI 0.72 to 1.67; p=0.68) and longer OS than Gem/NabP (HR 1.68, 95% CI 1.03 to 2.75; p=0.04). Median PFS was 5.0 months for both NALIRIFOX and mFOLFIRINOX and 4.3 months for Gem/NabP; NALIRIFOX showed longer PFS than Gem/NabP (HR 1.63, 95% CI 1.05 to 2.50; p=0.03), while PFS was similar between NALIRIFOX and mFOLFIRINOX. ORR was 37.5% for NALIRIFOX, 23.8% for mFOLFIRINOX and 40.5% for Gem/NabP. Recorded grade ≥3 toxicities appeared lower with NALIRIFOX, although cross-regimen safety comparisons were limited by retrospective toxicity ascertainment and likely differential reporting. Baseline carbohydrate antigen 19-9 remained imbalanced after matching because it was not included in the propensity model. Conclusion: In this multicentre real-world matched cohort of advanced PDAC, NALIRIFOX and mFOLFIRINOX were associated with comparable survival outcomes, and both were associated with more favourable survival than Gem/NabP. Recorded grade ≥3 toxicities appeared lower with NALIRIFOX, but safety findings should be interpreted cautiously because of retrospective toxicity capture and residual confounding. Prospective studies are needed to validate these findings.
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