In the French phase II PANACHE01-PRODIGE48 trial, researchers found that neoadjuvant chemotherapy with mFOLFIRINOX (modified leucovorin, fluorouracil, irinotecan, and oxaliplatin) was feasible and active in patients with resectable pancreatic adenocarcinoma. Schwarz et al published these findings in the Journal of Clinical Oncology.
Study Details
In the multicenter trial, 150 eligible patients were randomly assigned 2:2:1 between February 2017 and July 2020 to receive four cycles of neoadjuvant chemotherapy with mFOLFIRINOX (n = 72), four cycles of neoadjuvant chemotherapy with FOLFOX (leucovorin, fluorouracil, and oxaliplatin; n = 50), or upfront surgery followed by adjuvant chemotherapy (n = 28). The dual primary outcome measures were 1-year overall survival and proportions of patients in neoadjuvant chemotherapy groups completing the full therapeutic sequence (more than two cycles of treatment followed by surgical resection).
Key Findings
The primary objectives were achieved in the mFOLFIRINOX group.
The therapeutic sequence was completed by 70.8% (90% confidence interval [CI] = 60.8%–79.6%) of patients in the mFOLFIRINOX group and 68% (90% CI = 55.5%–78.8%) of those in the FOLFOX group.
At 12 months after randomization, 84.3% (90% CI = 75.3%–90.9%) of those in the mFOLFIRINOX group and 71.4% (90% CI = 59.0%–81.8%) of those in the FOLFOX group were alive.
The FOLFOX group was stopped at interim analysis for lack of efficacy: observation of eight patient deaths and noncompletion of two or more chemotherapy cycles.
Event-free survival at 1 year was 51.4% (95% CI= 41.0%–64.3%) in the mFOLFIRINOX group, 43.1% (95% CI = 31.3%–59.5%) in the FOLFOX group, and 38.7% (95% CI = 24.1%–62.0%) in the upfront surgery group.
Grade 3 or 4 chemotherapy toxicity occurred in 47% of the mFOLFIRINOX group and 37.8% of the FOLFOX group. No deaths due to chemotherapy toxicity were observed.
The investigators concluded, “The feasibility and efficacy of mFOLFIRINOX in the perioperative setting are confirmed concerning therapeutic sequence completion and oncologic outcomes, supporting ongoing trials (PREOPANC-3, Alliance AO21806). Further research is needed to identify patients who benefit from neoadjuvant chemotherapy.”
Lilian Schwarz, PhD, of the Department of Digestive Surgery, Rouen University Hospital, is the corresponding author for the Journal of Clinical Oncology.
Disclosure: The study was supported by a Clinical Research Hospital Program grant from the French Ministry of Health and the Institut National du Cancer. For full disclosures of the study authors, visit ascopubs.org.
