In a Dutch phase III trial (PREOPANC-2) reported in The Lancet Oncology, Janssen et al found no difference in overall survival between patients receiving neoadjuvant FOLFIRINOX vs neoadjuvant gemcitabine-based chemoradiotherapy for resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC).
Study Details
In the multicenter open-label trial, 375 patients were randomly assigned between June 2018 and January 2021 to receive neoadjuvant FOLFIRINOX (n = 188) or chemoradiotherapy (CRT; n = 187).
FOLFIRINOX consisted of oxaliplatin at 85 mg/m², irinotecan at 180 mg/m², leucovorin at 400 mg/m², followed by a 400 mg/m² fluorouracil bolus and then continuous infusion at 2,400 mg/m² over 46 hours every 14 days for eight cycles; subsequent surgery was not followed by adjuvant treatment.
CRT consisted of gemcitabine at 1,000 mg/m² on days 1, 8, and 15 of each 28-day cycle and on days 1 and 8 only in cycles 1 and 3, combined with hypofractionated radiotherapy at 36 Gy in 15 fractions during the second cycle only, followed by surgery and four cycles of adjuvant gemcitabine.
The primary endpoint was overall survival in the modified intention-to-treat population, consisting of 185 patients in the FOLFIRINOX group and 184 in the CRT group.
Key Findings
In the modified intention-to-treat population, after a median follow-up of 42.3 months (interquartile range = 35.7–48.7 months), median overall survival was 21.9 months (95% confidence interval [CI] = 17.7–27.0) in the FOLFIRINOX group vs 21.3 months (95% CI = 16.8–25.5 months) in the CRT group (hazard ratio [HR] = 0.88, 95% CI = 0.69–1.13, P = .32). Rates at 1 and 3 years were 76% vs 70% and 36% vs 33%, respectively.
Hazard ratios for overall survival were 0.93 (95% CI = 0.69–1.26, P = .64) among patients with resectable disease and 0.80 (95% CI = 0.53–1.21, P = .30) among those with borderline resectable disease.
Median progression-free survival was 12.1 months (95% CI = 11.3–15.0 months) in the FOLFIRINOX group vs 11.9 months (95% CI = 10.0–13.7 months) in the CRT group (HR = 0.84, 95% CI = 0.67–1.06, P = .14).
Grade ≥ 3 adverse events occurred in 67% of the FOLFIRINOX group vs 60% of the CRT group (P = .20); the most common were neutropenia (25%) and diarrhea (23%) in the FOLFIRINOX group and neutropenia (22%) and leukopenia (15%) in the CRT group. Serious adverse events occurred in 49% vs 43% of patients. Treatment-related death occurred in two patients in the FOLFIRINOX group (due to multiorgan failure and intestinal mucositis) and one patient in the CRT group (due to upper gastrointestinal hemorrhage).
The investigators concluded: “This randomized trial did not show a difference in overall survival between neoadjuvant FOLFIRINOX and neoadjuvant gemcitabine-based chemoradiotherapy in patients with resectable or borderline resectable PDAC. Both neoadjuvant treatment regimens may be considered in these patients.”
Bas Groot Koerkamp, MD, of the Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Dutch Cancer Society and ZonMw. For full disclosures of all study authors, visit thelancet.com.
