Background
Phase II/III RCT included 342 treatment-naïve patients with metastatic pancreatic adenocarcinoma and ECOG performance status 0-1. First-line setting.
Interventions and follow up
Arm A: FOLFIRINOX q2wk (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 180 mg/m², fluorouracil 400 mg/m² bolus then 2400 mg/m² 46h infusion)
Arm B: Gemcitabine 1000 mg/m² qwk x7, 1 wk off, then D1,8,15 q4wk
Primary endpoint: OS
mFollow up: 26.6 mo
Arm B: Gemcitabine 1000 mg/m² qwk x7, 1 wk off, then D1,8,15 q4wk
Primary endpoint: OS
mFollow up: 26.6 mo
Results
mOS: 11.1 vs 6.8 mo, arm A vs B (HR 0.57; 95% CI 0.45-0.73; P<.001)
mPFS: 6.4 vs 3.3 mo (HR 0.47; 95% CI 0.37-0.59; P<.001)
ORR: 31.6% vs 9.4% (P<.001)
6-mo OS: 75.9% vs 57.6%
12-mo OS: 48.4% vs 20.6%
18-mo OS: 18.6% vs 6.0%
mPFS: 6.4 vs 3.3 mo (HR 0.47; 95% CI 0.37-0.59; P<.001)
ORR: 31.6% vs 9.4% (P<.001)
6-mo OS: 75.9% vs 57.6%
12-mo OS: 48.4% vs 20.6%
18-mo OS: 18.6% vs 6.0%
Adverse events
Hematologic (grade ≥3, A vs B): neutropenia 45.7% vs 21.0%, febrile neutropenia 5.4% vs 1.2%, thrombocytopenia 9.1% vs 3.6%
Non-hematologic (grade ≥3, A vs B): diarrhea 12.7% vs 1.8%, sensory neuropathy 9.0% vs 0%, fatigue 23.6% vs 17.8%
Non-hematologic (grade ≥3, A vs B): diarrhea 12.7% vs 1.8%, sensory neuropathy 9.0% vs 0%, fatigue 23.6% vs 17.8%
Conclusions
FOLFIRINOX was superior to gemcitabine for first-line treatment of metastatic pancreatic cancer in patients with good performance status, at the cost of greater toxicity.
Key Limitations
Restricted to ECOG 0-1 and age ≤75; results not generalizable to frail or older patients. Increased toxicity necessitates careful patient selection; modified FOLFIRINOX commonly used in practice.
Clinical Context
FOLFIRINOX is an established first-line standard for metastatic pancreatic cancer in fit patients. ESMO recommends FOLFIRINOX for patients with ECOG 0-1; gemcitabine-based regimens for those with poorer performance status.