FOLFIRINOX Improves PFS in Locally Advanced Pancreatic Cancer

"The fact that this study showed a significant difference in its primary end point and the [ORR] suggests that FOLFIRINOX should be considered as a standard of care for LAPC in fit patients," according to the study authors.

Fluorouracil plus oxaliplatin and irinotecan (FOLFIRINOX) elicited a significant progression-free survival (PFS) improvement vs gemcitabine among patients with locally advanced pancreatic cancer (LAPC), according to findings from the phase 3 PRODIGE 29-UCGI 26 or NEOPAN trial (NCT02539537) published in the Journal of Clinical Oncology.1

Data showed a median PFS of 7.7 months (95% CI, 6.2-9.2) in the gemcitabine arm compared with 9.7 months (95% CI, 7.0-11.7) in the FOLFIRINOX arm (HR, 0.66; 95% CI, 0.46-0.95; P = .02). In each respective arm, the 12-month PFS rates were 17.4% vs 36.5%, the 24-month rates were 3.5% vs 5.9%, and the 36-month rates were 1.2% vs 3.5%.

Gemcitabine produced a median overall survival (OS) of 15.4 months (95% CI, 11.7-18.6) vs 15.7 months (95% CI, 11.9-20.4) with FOLFIRINOX (HR, 1.00; 95% CI, 0.69-1.44; P = .99). In each respective arm, the OS rates were 60.5% vs 61.2% at 12 months, 26.1% vs 27.1% at 24 months, and 12.3% vs 11.8% at 36 months.

The objective response rate (ORR) was 15.1% (95% CI, 8.3%-24.5%) in the gemcitabine arm, which included 2 complete responses (CRs), vs 42.4% (95% CI, 31.7%-53.6%) in the FOLFIRINOX arm, which included 8 CRs. Following study treatment, 9 patients—including 4 who received gemcitabine and 5 who received FOLFIRINOX—had surgery. A pathologist-confirmed R0 resection of the pancreatic tumor occurred in 4.7% (95% CI, 1.3%-11.0%) of patients in the gemcitabine arm and 5.9% (95% CI, 1.9%-13.0%) of those in the FOLFIRINOX arm.

“The fact that this study showed a significant difference in its primary end point and the [ORR] suggests that FOLFIRINOX should be considered as a standard of care for LAPC in fit patients,” lead study author Michel Ducreux, MD, PhD, from Gustave Roussy Cancer Center, Tumor Cells Dynamics, INSERM U1279, Université Paris-Saclay in Villejuif, France, wrote with coauthors.1 “The absence of a clear difference in OS suggests that an initial advantage provided by a more intensive treatment may be made up secondarily, making it possible to consider a milder treatment such as gemcitabine monotherapy in patients whose general condition is initially more impaired and who may subsequently receive FOLFIRINOX if they become metastatic.”

In this multicenter phase 3 trial, a total of 171 patients were randomly assigned 1:1 to receive gemcitabine at 1000 mg/m2 (n = 86) or FOLFIRINOX (n = 85). Treatment with FOLFIRINOX consisted of oxaliplatin at 85 mg/m2 and leucovorin at 400 mg/m2 given as 2-hour infusions, irinotecan at 180 mg/m2 via a 90-minute infusion through a Y-connector, and fluorouracil at 2400 mg/m2 over 46 hours biweekly.

The trial’s primary end point was PFS. Secondary end points included OS, time to treatment failure, ORR per RECIST v1.1 criteria, composite index for treatment early severe toxicity, adverse effects (AEs), and quality of life (QOL).2

Patients 18 years or older with histologically or cytologically confirmed adenocarcinoma of the pancreas and locally advanced and unresectable tumors were eligible for enrollment on the study. Other eligibility criteria included having adequate vital function and a WHO performance status of 0 or 1.

The median age was 68 years (range, 43-81) in the gemcitabine arm and 68 years (range, 42-84) in the FOLFIRINOX arm. Additionally, most patients in each arm had an ECOG performance status of 1 (55% vs 56%), adenocarcinoma histology (99% vs 100%), and pancreatic head tumors (56% vs 47%). A numerically higher proportion of patients were female in the gemcitabine arm (53%) compared with the FOLFIRINOX arm (47%).

In the gemcitabine and FOLFIRINOX arms, respectively, 7 and 1 died due to treatment-related causes. Additionally, 8% and 7% of patients in each arm discontinued therapy following AEs. Grade 3 or 4 serious AEs occurred in 27% and 5% of the gemcitabine arm compared with 36% and 5% of the FOLFIRINOX arm. In each respective arm, the most common grade 3/4 AEs included neutropenia (33% vs 13%), diarrhea (5% vs 18%), and fatigue (5% vs 18%).

Among patients with evaluable responses to the QLQ-C30 questionnaire, investigators reported no significant differences regarding the global health status and QOL scale across the gemcitabine and FOLFIRINOX arms.

References

1. 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
2. A randomized phase III trial comparing FOLFIRINOX to gemcitabine in locally advanced pancreatic carcinoma (NEOPAN). ClinicalTrials.gov. Updated January 9, 2024. Accessed May 28, 2025. https://tinyurl.com/bdfdtunx