Background
Systematic review and meta-analysis. Identified 13 studies reporting outcomes of FOLFIRINOX or modified FOLFIRINOX for locally advanced pancreatic cancer (LAPC), including 689 patients across 13 institutions in 8 countries. Pooled analysis to characterize the efficacy of FOLFIRINOX-based systemic therapy in this setting.
Interventions and follow up
Arm A: FOLFIRINOX or modified FOLFIRINOX (heterogeneous doses across studies)
Arm B: N/A — systematic review without comparator
Primary endpoint: Pooled overall survival
Median follow-up: Varied by study
Arm B: N/A — systematic review without comparator
Primary endpoint: Pooled overall survival
Median follow-up: Varied by study
Results
mOS: 24.2 months (95% CI 21.7–26.8)
mPFS: 15.0 months (95% CI 12.9–18.2)
ORR: 31.4% (95% CI 26.3–37.1)
Resection rate: 28.1% (95% CI 20.7–37.0)
mPFS: 15.0 months (95% CI 12.9–18.2)
ORR: 31.4% (95% CI 26.3–37.1)
Resection rate: 28.1% (95% CI 20.7–37.0)
Adverse events
Hematologic: Pooled grade 3/4 neutropenia 29.6%.
Non-hematologic: Grade 3/4 fatigue 16.2%, nausea 8.6%, peripheral neuropathy 6.0%; treatment discontinuation for toxicity ~10%.
Non-hematologic: Grade 3/4 fatigue 16.2%, nausea 8.6%, peripheral neuropathy 6.0%; treatment discontinuation for toxicity ~10%.
Conclusions
FOLFIRINOX achieved a pooled mOS of 24.2 months in LAPC — substantially longer than prior gemcitabine-based therapies (~8–13 months) and comparable to historical OS in resected disease. A 28% resection rate provides evidence of meaningful downstaging. FOLFIRINOX became the preferred induction regimen for fit LAPC patients.
Key Limitations
Meta-analysis of predominantly small retrospective and phase II studies with high heterogeneity across institutions, selection criteria, and FOLFIRINOX modifications. Lack of standardized criteria for resectability after induction. Publication bias likely inflates efficacy estimates. No randomized phase III trial directly compares FOLFIRINOX with gemcitabine-based therapy in LAPC. Conversion-to-resection rates may depend heavily on institutional surgical expertise.
Clinical Context
This meta-analysis established FOLFIRINOX as the standard induction regimen for LAPC, displacing gemcitabine-based chemoradiotherapy. Current practice (per ESMO) for fit LAPC patients: FOLFIRINOX or nab-paclitaxel + gemcitabine ×4–6 months, then restaging; if no progression, chemoradiotherapy, maintenance, or surgical evaluation. LAP07 showed chemoradiotherapy after induction does not improve OS but reduces local progression.
References