FOLFIRINOX Significantly Improves Progression-Free Survival for Patients With Locally Advanced Pancreatic Cancer

Results from the phase 3 NEOPAN trial demonstrated that fluorouracil plus oxaliplatin and irinotecan (FOLFIRINOX) significantly improved progression-free survival (PFS) compared to gemcitabine among patients with locally advanced pancreatic cancer. 

According to Michel Ducreux, MD, PhD, Gustave Roussy Cancer Center, Villejuif, France, and coauthors, “[FOLFIRINOX] has been shown to be more effective than gemcitabine in the first-line metastatic setting and in the adjuvant setting…this trial evaluated the value of FOLFIRINOX versus gemcitabine in [the] locally advanced [setting].” 

In this multicenter study, researchers randomized 169 chemotherapy-naive patients on a 1-to-1 basis to receive either 1000 mg/m² of gemcitabine based on body surface area once weekly for 7 weeks followed by 1 week off and once weekly again for 3 weeks in 4-week cycles (gemcitabine arm, n = 85) or 85 mg/m² of oxaliplatin and 400 mg/m² of leucovorin plus 180 mg/m² of irinotecan followed by 2400 mg/m² of fluorouracil once every 2 weeks (FOLFORINOX arm, n = 84). The primary end point was PFS. Secondary end points included overall survival (OS), objective response rate (ORR), and safety. 

At a median follow-up of 59.6 months, median PFS was 9.7 months in the FOLFIRINOX arm and 7.7 months in the gemcitabine arm (hazard ratio [HR] 0.7; 95% confidence interval [CI], 0.5 to 1.0; P = .04). Median OS was 15.7 months and 15.4 months (HR 1.02; 95% CI, 0.73 to 1.43; P = .95), respectively. The ORR was 42.4% with 8 complete responses in the FOLFIRINOX arm and 15.1% with 2 complete responses in the gemcitabine arm.

Treatment discontinuation due to any grade treatment-related adverse event occurred in 7% of patients in the FOLFIRINOX arm and 8% of patients in the gemcitabine arm. There were 8 treatment-related deaths including 1 in the FOLFIRINOX arm and 7 in the gemcitabine arm. The incidence of grade 3 serious adverse events was 36% in the FOLFIRINOX arm and 27% in the gemcitabine arm and the incidence of grade 4 serious adverse events was 5% in both arms.

“Results confirm that FOLFIRINOX improves PFS significantly compared with gemcitabine and is well tolerated,” concluded Dr Ducreux et al. “No significant difference in OS was observed between both groups.”

“Next steps are moving beyond cytotoxic therapy including the integration of KRAS targeted therapy and late stage trials are underway,” added Journal of Clinical Oncology associate editor Eileen M. O'Reilly, MD, Memorial Sloan Kettering Cancer Center, New York, New York. 

Source: 

Ducreux M, Desgrippes R, Rinaldi Y, et al. PRODIGE 29-UCGI 26 (NEOPAN): A phase III randomized trial comparing chemotherapy with FOLFIRINOX or gemcitabine in locally advanced pancreatic carcinoma. J Clin Oncol. Published online: May 16, 2025. doi: 10.1200/JCO-24-02210