PRODIGE 29-UCGI 26 (NEOPAN): A Phase III Randomized Trial Comparing Chemotherapy With FOLFIRINOX or Gemcitabine in Locally Advanced Pancreatic Carcinoma.

PURPOSE More than 30% of patients with pancreatic cancer are unresectable because of the local extension with a median overall survival (OS) of <1 year. Combination of fluorouracil (FU), oxaliplatin, and irinotecan (FOLFIRINOX) is superior to gemcitabine in the treatment of metastatic pancreatic cancer, but standard of care remains gemcitabine in locally advanced pancreatic cancer (LAPC). METHODS Patients with histologically proven LAPC not suitable for surgery, Eastern Cooperative Oncology Group WHO performance status (PS) ≤1 were eligible. Random assignment was stratified by center, tumor localization (pancreas head yes/no), WHO PS (0 v 1), and age (≤60 years v >60 years). Patients received FOLFIRINOX or gemcitabine for 6 months. The primary end point was progression-free survival (PFS). Main secondary end points were OS, time to treatment failure, quality of life, and safety. One hundred seventy patients (142 events) were needed to detect an increase of 3 months in PFS with 80% power (log-rank test, 5% two-sided α). RESULTS One hundred seventy one patients age 35-84 years were included and followed for a maximum of 5 years. With a median follow-up of 59.6 months (95% CI, 42.3 to not reached), 168 events were observed and the median PFS was 9.7 months (95% CI, 7.0 to 11.7) with FOLFIRINOX versus 7.7 months (95% CI, 6.2 to 9.2) with gemcitabine, hazard ratio (HR), 0.7 (95% CI, 0.5 to 1.0), P = .04. The median OS was 15.7 months (95% CI, 11.9 to 20.4) in the FOLFIRINOX group versus 15.4 months (95% CI, 11.7 to 18.6) in the gemcitabine group, HR, 1.02 (95% CI, 0.73 to 1.43), P = .95. CONCLUSION Results confirm that FOLFIRINOX improves PFS significantly compared with gemcitabine and is well tolerated in LAPC. No significant difference in OS was observed between both groups.