Adjuvant FOLFIRINOX vs Gemcitabine in Pancreatic Cancer
In a phase III Canadian and French trial reported in The New England Journal of Medicine, Conroy and colleagues in the Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group found that adjuvant modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) produced better disease-free and overall survival than gemcitabine in patients with resected pancreatic cancer.
Study Details
In the open-label trial, 493 patients from 77 sites in France and Canada were randomly assigned between April 2012 and October 2016 to receive adjuvant therapy with modified FOLFIRINOX (n = 247) or gemcitabine (n = 246). The FOLFIRINOX regimen consisted of oxaliplatin at 85 mg/m2; irinotecan at 180 mg/m2, which was reduced to 150 mg/m2 after a protocol-specified safety analysis; leucovorin at 400 mg/m2; and fluorouracil at 2,400 mg/m2 every 2 weeks for 24 weeks. Gemcitabine was given at 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks for 24 weeks. Randomization was stratified for trial center, lymph node status, resection status, and CA 19-9 level.
The primary endpoint was disease-free survival in the intent-to-treat population.
Survival Findings
At a median follow-up of 33.6 months, median disease-free survival was 21.6 months in the modified FOLFIRINOX group vs 12.8 months in the gemcitabine group (stratified hazard ratio [HR] = 0.58, P < .001). Disease-free survival at 3 years was 39.7% vs 21.4%.
Median overall survival was 54.4 months vs 35.0 months (stratified HR = 0.64, P = .003). Overall survival at 3 years was 63.4% vs 48.6%. Median metastasis-free survival was 30.4 months vs 17.7 months (stratified HR = 0.59, P < .001). Postrelapse treatments consisted of chemotherapy in 63.0% vs 75.7%, radiotherapy with or without chemotherapy in 12.6% vs 5.9%, and surgery in 4.7% vs 4.7%.
Toxicity
Grade 3 or 4 adverse events occurred in 75.9% of the FOLFIRINOX group vs 52.9% of the gemcitabine group. Grade 3 or 4 diarrhea, increased γ-glutamyltransferase level, paresthesia, fatigue, sensory peripheral neuropathy, nausea, vomiting, abdominal pain, and mucositis were more common in the FOLFIRINOX group; grade 3 or 4 thrombocytopenia was more common in the gemcitabine group. The occurrence of neutropenia was similar in the two groups (67% vs 64% for any grade), but granulocyte colony-stimulating factor was required in 62.2% vs 3.7% of patients (P < .001), representing 41.8% vs 1.1% of cycles.
The investigators concluded, “Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects.”
Disclosure: The study was funded by R&D Unicancer and others. The study authors’ full disclosures can be found at nejm.org.
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