Adjuvant therapy with mFOLFIRINOX—a modified regimen of oxaliplatin, leucovorin, irinotecan, and fluorouracil (5-FU)—significantly prolonged disease-free survival (DFS) and overall survival (OS) in patients with nonmetastatic pancreatic ductal adenocarcinoma (PDAC). These are the findings of a multicenter French and Canadian study (LBA4001) that represents the first trial to demonstrate a large benefit from adjuvant FOLFIRINOX chemotherapy over standard chemotherapy with gemcitabine.
Median OS was 54.5 months with mFOLFIRINOX compared with 35 months with gemcitabine, the current standard of care. Similarly, median DFS with mFOLFIRINOX and gemcitabine was 21.6 months vs 12.8 months, respectively.
“mFOLFIRINOX should now be considered a new standard of care after pancreatic cancer resection in patients with good performance status,” said lead study author Thierry Conroy, MD, director of the Institut de Cancerologie de Lorraine in Nancy. Conroy presented the results at a press conference at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
“The median survival with [modified] FOLFIRINOX is the best ever achieved with any adjuvant treatment, and there was a 15% increase in survival at 3 years,” Conroy said.
Gemcitabine and/or fluoropyrimidine have been recognized as standard adjuvant treatments for resected pancreatic cancer, but given that 71% to 76% of patients still relapse within 2 years despite these treatments, there is an obvious need for a better regimen to cure patients, explained Conroy.
FOLFIRINOX has proven more effective than gemcitabine as frontline treatment for metastatic pancreatic cancer in patients with good performance status, but it could be too toxic for use in the adjuvant setting. Thus, a modified regimen was developed that omitted the fluorouracil bolus, which reduced hematologic toxicities and diarrhea but maintained similar efficacy.
The phase III PRODIGE trial randomized 493 patients with resected PDAC to receive gemcitabine (given in 28-day cycles on days 1, 8, and 15 for 6 cycles) or mFOLFIRINOX (oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², irinotecan at 150 mg/m² on day 1, and 5-fluoroucil at 2.4 g/m² over 46 hours) every 14 days for 12 cycles.
At a median follow-up of 33.6 months, median DFS was 12.8 months (95% CI, 11.7–15.2) for the gemcitabine group vs 21.6 months (95% CI, 17.5–26.7) for mFOLFIRINOX (hazard ratio [HR], 0.59; 95% CI, 0.47–0.74). The 3-year disease survival rate was 21.4% (95% CI, 15.8–27.5) in the gemcitabine group, but was nearly double that in the mFOLFIRINOX group at 39.7% (95% CI, 32.8–46.6).
Median OS was 35.0 months (95% CI, 28.7–43.9) for the gemcitabine group vs 54.4 months (95% CI, 41.8 to not reached [NR]) in the mFOLFIRINOX group, a difference of almost 20 months. The 3-year OS was also superior for FOLFIRINOX; 63.4% vs 48.6%.
Median metastasis-free survival was 17.7 months (95% CI, 14.2–21.5) and 30.4 months (95% CI, 21.7–NR), favoring mFOLFIRINOX.
“The superiority of FOLFIRINOX was observed in all predefined patient subgroups,” said Conroy, adding that even though FOLFIRINOX was more toxic than gemcitabine, it is still a safe regimen with manageable toxicities.
ASCO Expert Andrew Epstein, MD, from Memorial Sloan Cancer Center in New York City, agrees that this does represent a new standard of care in this setting. “There was a significant improvement in survival for a notoriously aggressive disease,” he said, and emphasized that it is important that this chemotherapy regimen be administered to patients with a good performance status.
“It would be tempting to give this to anyone after surgery, but it is a relatively challenging regimen and we want to make sure we recommend it to patients who can withstand the rigorousness of this treatment,” he said.