In a French phase III trial (NEOPAN) reported in the Journal of Clinical Oncology, Ducreux et al evaluated whether FOLFIRINOX (fluorouracil, oxaliplatin, and irinotecan) significantly improved progression-free survival vs gemcitabine in patients with locally advanced pancreatic carcinoma not suitable for surgery.
Study Details
In the multicenter trial, 171 patients were randomly assigned between March 2015 and January 2022 to receive 6 months of treatment with FOLFIRINOX (n = 85; oxaliplatin at 85 mg/m2, leucovorin at 400 mg/m2, and irinotecan at 180 mg/m2, followed by continuous infusion of fluorouracil at 2,400 mg/m2 over 46 hours every 2 weeks) or gemcitabine (n = 86; 1,000 mg/m2 once weekly for 7 weeks, followed by a 1-week rest, then once weekly for 3 weeks in subsequent 4-week cycles). The primary endpoint was progression-free survival.
Key Findings
Patients were followed for a maximum of 5 years. At a median follow-up of 59.6 months (95% confidence interval [CI] = 42.3 months to not reached), median progression-free survival was 9.7 months (95% CI = 7.0–11.7 months) in the FOLFIRINOX group vs 7.7 months (95% CI = 6.2–9.2 months) in the gemcitabine group (hazard ratio [HR] = 0.7, 95% CI = 0.5–1.0, P = .04). Rates at 12, 24, and 36 months were 36.5% vs 17.4%, 5.9% vs 3.5%, and 3.5% vs 1.2%.
In patients with disease progression, 77% of those in the FOLFIRINOX group and 64% of those in the gemcitabine group received second-line chemotherapy. Median overall survival was 15.7 months (95% CI = 11.9–20.4 months) in the FOLFIRINOX group vs 15.4 months (95% CI = 11.7–18.6 months) in the gemcitabine group (HR = 1.02, 95% CI = 0.73–1.43, P = .95).
The most common grade 3 or 4 adverse events were diarrhea (18%) and fatigue (18%) in the FOLFIRINOX group and neutropenia (13%) in the gemcitabine group. Adverse events led to death in one patient in the FOLFIRINOX group (from deterioration of general status) and in seven patients in the gemcitabine group (from deterioration of general status in three and digestive hemorrhage, cholecystitis, malignant arterial hypertension, and liver abscess in one each).
The investigators concluded: “Results confirm that FOLFIRINOX improves [progression-free survival] significantly compared with gemcitabine and is well tolerated in [locally advanced pancreatic cancer]. No significant difference in [overall survival] was observed between…groups.”
Michel Ducreux, MD, PhD, of the Gustave Roussy Cancer Center, Tumor Cells Dynamics, INSERM, Université Paris-Saclay, Villejuif, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a Clinical Research Hospital Program grant from the French Ministry of Health, Institut National du Cancer, La Ligue Nationale Contre le Cancer, and others. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
