Impact of ERCC1 on the outcomes of chemotherapy in advanced biliary tract cancer.

The phase III randomized trial, JCOG1113 has demonstrated the non-inferiority of gemcitabine and S-1 (GS) therapy to gemcitabine and cisplatin (GC) therapy for advanced biliary tract cancer (BTC). However, biomarkers for favorable therapy or to predict patient prognosis remain lacking. In this study, we evaluated five candidate biomarkers potentially involved in the efficacy of cisplatin or S-1 by immunostaining tumor specimens obtained from JCOG1113 participants. The participants were randomly divided into training or test sets and classified into high- or low-expression groups based on the cutoff value calculated from the immunostaining results for each biomarker in the training set. Associations between the expression of each biomarker and the outcomes in JCOG1113 were analyzed. Among the 148 eligible participants, no interaction was observed between the treatment arms of GC or GS for any factor or biomarker. However, high excision repair cross-complementing gene 1 (ERCC1) was associated with poor overall survival (HR, 2.226; 95% CI, 1.160-4.272) and progression-free survival (HR, 1.793; 95% CI, 0.945-3.402) compared with low ERCC1 in the training set. Similar trends were observed for the test set. Our results indicate that in advanced BTC, high ERCC1 expression is a poor prognostic factor.