Neoadjuvant FOLFIRINOX Did Not Significantly Improve Overall Survival Among Patients With Resectable or Borderline Resectable Pancreatic Ductal Adenocarcinoma
Key Clinical Takeaways
- Design/Population: In the phase 3, open-label PREOPANC-2 trial, 369 patients with resectable or borderline resectable pancreatic ductal adenocarcinoma were randomized 1:1 to neoadjuvant FOLFIRINOX followed by surgery (n = 185) or gemcitabine plus hypofractionated radiotherapy followed by surgery and adjuvant gemcitabine (n = 184).
- Key Outcomes: After a median 42.3-month follow-up, median OS was 21.9 months with FOLFIRINOX vs 21.3 months with chemoradiotherapy (HR 0.88; 95% CI, 0.69–1.13; P = .32). Grade ≥3 adverse events occurred in 67% vs 60% of patients (P = .20), with neutropenia, diarrhea, and leukopenia most common.
- Clinical Relevance: Neoadjuvant FOLFIRINOX did not significantly improve OS compared with gemcitabine-based chemoradiotherapy, indicating both regimens remain viable options for resectable or borderline resectable pancreatic cancer.
Results from the phase 3 PREOPANC-2 trial demonstrated that neoadjuvant FOLFIRINOX did not significantly improve overall survival (OS) results compared to neoadjuvant gemcitabine-based chemoradiotherapy among patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.
In this open-label, investigator-initiated trial, 369 patients were randomized on a 1-to-1 basis to receive either FOLFIRINOX followed by surgical resection without adjuvant treatment (n = 185) or gemcitabine plus hypofractionated radiotherapy followed by surgical resection and 4 cycles of adjuvant gemcitabine (n = 184). The primary end point was OS. A key secondary end point was safety.
At a median follow-up of 42.3 months, median OS was 21.9 months in the FOLFIRINOX arm and 21.3 months in the chemoradiotherapy arm (hazard ratio [HR] 0.88; 95% confidence interval [CI], 0.69 to 1.13; P = .32). The most common grade 3/4 adverse events included neutropenia, diarrhea, and leukopenia. Grade ≥ 3 adverse events occurred in 67% of patients in the FOLFIRINOX arm and 60% of patients in the chemoradiotherapy arm (P = .20). Serious adverse events occurred in 49% and 43% of patients, respectively (P = .26). Three treatment-related deaths were reported: 2 in the FOLFIRINOX arm due to multi-organ failure and intestinal mucositis and 1 in the chemoradiotherapy arm due to upper gastrointestinal hemorrhage.
“This randomised trial did not show a difference in overall survival between neoadjuvant FOLFIRINOX and neoadjuvant gemcitabine-based chemoradiotherapy in patients with resectable or borderline resectable [pancreatic ductal adenocarcinoma],” concluded Dr Janssen et al. “Both neoadjuvant treatment regimens may be considered in these patients.”
Source:
Janssen QP, Van Dam JL, Van Bekkum ML, et al. Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): A multicentre, open-label, phase 3 randomised trial. Lancet Oncol. Published online: September 10, 2025. doi: 10.1016/S1470-2045(25)00363-8
