Adjuvant FOLFIRINOX versus S-1 monotherapy for resected PDAC: retrospective real-world data.

BACKGROUND: Although modified FOLFIRINOX (mFOLFIRINOX) has improved survival in patients with resected pancreatic ductal adenocarcinoma (PDAC) in clinical studies, S-1 is also a treatment option with desirable efficacy and limited toxicity. We aimed to compare the efficacy and safety of adjuvant mFOLFIRINOX with those of S-1 monotherapy for PDAC. OBJECTIVES: This study aimed to compare the efficacy and safety of adjuvant mFOLFIRINOX versus S-1 monotherapy in resected PDAC. DESIGN: A retrospective real-world study. METHODS: Patients with resected PDAC who received adjuvant mFOLFIRINOX or S-1 chemotherapy at Peking Union Medical College Hospital were reviewed. RESULTS: A total of 223 patients were included, with 141 receiving S-1 and 82 receiving mFOLFIRINOX. Patients who received mFOLFIRINOX were younger (median age: 55.5 vs 66 years, p < 0.001) and had a significantly lower proportion of early-stage disease (stage I: 20.7% vs 46.1%, p < 0.001). The median disease-free survival (18.1 vs 12.5 months, p = 0.021) and overall survival (51.4 vs 24.7 months, p = 0.006) of the mFOLFIRINOX group were significantly longer, even after adjustment for bias. However, the incidence of grade 3 or 4 adverse events (65.0% vs 39.4%, p = 0.007), especially fatigue and gastrointestinal toxicity, was greater in the mFOLFIRINOX group than in the S-1 group. Furthermore, the molecular features of the included patients were also explored, and KMT2D alterations may be prognostic indicators of poor survival outcomes. No correlation between alterations in the homologous recombination repair-related genes and prognosis was observed in postoperative patients with PDAC. CONCLUSION: The mFOLFIRINOX regimen as an adjuvant chemotherapy for patients with resected PDAC demonstrated better efficacy than did S-1 monotherapy.