Neoadjuvant FOLFIRINOX versus adjuvant gemcitabine in pancreatic cancer.

4123 Background: In the metastatic or adjuvant setting for pancreatic cancer, the combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in longer overall survival (OS) compared to gemcitabine therapy. We conducted an institutional study to compare the efficacy of neoadjuvant modified FOLFIRINOX (neo-mFOLFIRINOX) to adjuvant gemcitabine (adj-gem) for pancreatic cancer patients who completed resection. Methods: The study retrospectively enrolled patients from 2006 to 2017 from Ohio State University. While patients who received adjuvant gemcitabine were considered to be resectable upfront, patients who received neo-mFOLFIRINOX were either staged as borderline resectable (BR) or un-resectable (UR) by the institutional tumor board group. 111 patients received adj-gem (average cycles, 5.5) and 52 patients received neo-mFOLFIRINOX (average cycles, 3.5). The survival rates were determined by the Kaplan-Meier method and analyzed using Cox regression and log-rank test. Results: At a median follow up of 21.3 months, the median OS was 35.4 months in the neo-mFOLFIRINOX group and 21.8 months in the adj-gem group (hazard ratio, 0.56, 95% confidence interval (CI), 0.37-0.84 p = 0.005). The OS rate at 3 years was 46% in the neo-mFOLFIRINOX group and 22% in the adjuvant gemcitabine group (p = 0.001). The median disease free survival (DFS) was 18.6 months in the neo-mFOLFIRINOX group and 12.0 months in the adj-gem group (hazard ratio, 0.63, 95% CI, 0.43-0.93 p = 0.022). The DFS rate at 3 years was 17% in the neo-mFOLFIRINOX group and 11% in the adj-gem group (p = 0.02). On surgical pathological specimen review, the neo-mFOLFIRINOX group had statistically (p < 0.05) lower tumor grade, lower rates of perineural invasion and lymphovascular invasion, lower pathological T stage, lower pathological N stage, and lower number of nodes positive compared to the adj-gem group. Frequencies of obtaining R0 resections were higher in the neo-mFOLFIRINOX versus adj-gem groups but not statistically different (51.9% vs 40.4, p = 0.2). The average age and performance status were similar between the two groups. Conclusions: At our institution, BR and UR pancreatic cancer patients who received neo-mFOLFIRINOX and completed resection had longer OS, DFS, and more favorable pathological indicators compared to those patients who had upfront surgery and adjuvant gemcitabine. Randomized clinical trials comparing neoadjuvant versus adjuvant FOLFIRINOX are needed to validate these findings.