FOLFIRINOX goes adjuvant

Owing to a 5-year survival of only ~10% after surgery, the standard-of-care treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC) involves adjuvant chemotherapy with gemcitabine or a fluoropyrimidine. Fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX), a regimen associated with better outcomes than gemcitabine in the metastatic setting, has now been associated with favourable survival outcomes in the adjuvant setting.

In a phase III trial, patients with resected PDAC and no evidence of metastatic disease were randomly allocated to treatment with modified FOLFIRINOX (n = 247) or gemcitabine (n = 246). The median disease-free survival duration was longer with FOLFIRINOX than with gemcitabine (21.6 months versus 12.8 months; P < 0.001). Subgroup analyses revealed significant benefits with FOLFIRINOX across all patient subsets, except that comprising patients older than 70 years (20.5% of the trial population).

The superiority of FOLFIRINOX over gemcitabine was also observed in comparisons of overall survival (OS; median duration of 54.4 months versus 35.0 months; P = 0.003). Of note, median OS with gemcitabine was longer in this trial than in other trials of adjuvant gemcitabine (20.1–26.5 months). This finding might be related to the high percentage of patients in the gemcitabine group (76%) that crossed over to receive FOLFIRINOX after disease relapse.

Grade 3–4 adverse events (AEs) were reported in 75.9% and 52.9% of patients in the FOLFIRINOX and gemcitabine groups, respectively; most of these toxicities were manageable. The regimens differed in their toxicity profiles — among the differences, grade 3–4 diarrhoea affected 18.6% of patients treated with FOLFIRINOX versus 3.7% of patients in the gemcitabine group.

The survival outcomes observed in this study favour adjuvant FOLFIRINOX as a new therapeutic option for patients with PDAC. The weight of factors (such as toxicity profiles or patient age) will need to be considered in decision-making processes when this regimen is adopted in routine clinical practice.