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Adjuvant FOLFIRINOX vs Gemcitabine in Pancreatic Cancer

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Key Points

  • Adjuvant modified FOLFIRINOX was associated with improved disease-free and overall survival vs gemcitabine.
  • Severe adverse events were more common with FOLFIRINOX.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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