Predictive value of ERCC1, ERCC2, ERCC4, and glutathione S-transferase P1 for FOLFIRINOX in unresectable pancreatic cancer

Background FOLFORINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) is one of the current standard chemotherapy, along with gemcitabine plus nab-paclitaxel, for unresectable pancreatic cancer. However, it has a high level of toxicity including neutropenia and febrile neutropenia and has limitation in its indication. Presently, there are no predictive biomarkers for FOLFIRINOX. A correlation between increased excision repaircross-complementing1(ERCC1)expressionandnonresponsetoFOLFOXhasbeen reported for colon cancer. Therefore, in this study, we examined the expression of ERCC1, ERCC2,ERCC4,andGlutathioneS-TransferaseP1(GSTP1)aspredictivebiomarkers related to sensitivity to platinum agents. Methods The study population consisted of 34 patients (median age, 61 years) with unresectable pancreatic cancer who were treated with FOLFIRINOX. The expressions of ERCC1, ERCC2, ERCC4, and GSTP1 were examined using immunohistochemistry. The clinical outcome was investigated in terms of overall survival (OS), progression-free survival (PFS), response rate (RR), disease control rate (DCR), and the frequency of grade 3 or 4 neutropenia. Whether some background factors, such as ECOG performancestatus(PS)andneutrophil-to-ymphocyteratio(NLR)contributedto clinical outcome was evaluated by the Cox proportional hazards model. Results ERCC1, ERCC2, ERCC4, and GSTP1 were positive in 64%, 24%, 18%, and 64% of cases. There were no significant differences between outcomes and the expression patterns. The frequency of grade 3 or 4 neutropenia also did not correlate with the expression patterns. Multivariate analysis revealed that ECOG PS of 1 significantly impacted OS (HR: 9.50, 95% CI: 2.25-40.07, P = 0.002) and PFS (HR: 4.95, 95% CI: 75-14.00, P = 0.003) compared with PS of 0, and the NLR ^5 affected OS (HR: 6.02, 95%CI:1.20-30.29,P=0.03). Conclusions ERCC1, ERCC2, ERCC4, and GSTP1 were unlikely to be predictive biomarkersofFOLFIRINOXinthissetting. Legal entity responsible for the study Shun Tezuka Funding Kanagawa Cancer Center Disclosure All authors have declared no conflicts of interest.