Impact of BRCAness on the efficacy of oxaliplatin-based chemotherapy in patients with unresectable pancreatic cancer.

Abstract

250 Background: Defects in individual genes that are involved in homologous recombination repair (HRR) is called “BRCAness” and several studies suggested that patients with BRCAness are more sensitive to platinum-based chemotherapy (Golan et al, 2014; Lowery et al, 2011; Vollebergh et al, 2014). We introduced the multiplex gene panel test into daily clinical practice since April 2015 at Kyoto University Hospital, in which we can monitor the entire coding region of 215 cancer-related genes and the rearrangement of 17 frequently rearranged genes. The purpose of this study was to evaluate the association between BRCAness status monitored by multiplex gene panel test and clinical outcome of patients with unresectable pancreatic ductal adenocarcinoma (PDAC) who received oxaliplatin-based chemotherapy. Methods: A total of consecutive 17 patients with histologically confirmed PDAC who underwent multiplex gene panel test were eligible. BRCAness status was determined according to the results of multiplex gene panel test. Oxaliplatin-based chemotherapy included FOLFIRINOX, GEMOX and SOX. We assessed the time to treatment failure (TTF) to evaluate the efficacy of oxaliplatin-based chemotherapy by log-rank test. Results: BRCAness-related mutations were detected in BRCA2 (n = 6), ATM (n = 4), ATR (n = 2), BRCA1 (n = 2), and PALB2 (n = 1). Based on these results, 11 patients were classified into non-BRCAness group and six patients were into BRCAness group. Seven and five patients received oxaliplatin-based chemotherapy in non-BRCAness and BRCAness group, respectively. Median TTF of oxaliplatin-based chemotherapy was 52 days (95% confidence interval [CI], 40–90 days) in non-BRCAness group and 294 days (95% CI, 56 days–NA) in BRCAness group. The difference was statistically significant (P = 0.027). Of note, two patients with BRCAness showed good response to FOLFIRINOX without disease progression > 500 days. Conclusions: BRCAness-related mutations could be a promising predictive marker of the efficacy of oxaliplatin-based chemotherapy.