Prognostic value of the mutation in patients with pancreatic ductal adenocarcinoma receiving FOLFIRINOX.

Background: , , , and have been the main driver mutations in pancreatic ductal adenocarcinoma (PDAC). Studies on the clinical significance and treatment response to 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen in terms of the presence of these mutations remain inconclusive.

Objectives: This study aimed to compare the survival outcome and response to FOLFIRINOX chemotherapy based on the presence of four driver mutation genes.

Design: A multi-center retrospective study conducted at two tertiary medical centers.

Methods: This study analyzed PDAC patients who were treated with FOLFIRINOX chemotherapy as the initial treatment. Tumor specimens were analyzed by a targeted next-generation sequencing platform at two tertiary referral hospitals from January 2016 to March 2022. Patients' demographics, survival outcomes, and chemotherapeutic response were investigated and compared according to the presence of driver mutations.

Results: The analysis included 100 patients. mutation was identified in 92 (92.0%) patients, followed by , , and in 63 (63.0%), 18 (18.0%), and 17 (17.0%) patients, respectively. The wild-type group demonstrated longer overall survival (OS) than the mutated group (median OS: 29 vs 19 months,  = 0.03), and served as a prognostic factor for survival (hazard ratio = 1.74, 95% confidence interval: 1.00-3.00,  = 0.048). The difference in OS according to mutation was intensified in localized pancreatic adenocarcinoma (37 vs 19 months,  = 0.01). The wild-type group demonstrated a higher objective response rate to FOLFIRINOX chemotherapy than the mutation group in localized pancreatic adenocarcinoma (50.0% vs 17.6%,  = 0.024).

Conclusion: PDAC patients with wild-type demonstrated longer OS than those with mutation, and this trend was intensified in patients with localized disease. This result may be due to an impaired response to FOLFIRINOX chemotherapy in patients with mutation.