Abstract 578: Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tract cancer

Abstract

Abstract BACKGROUND. We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX) resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers. Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS. EGFR, KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp reactions. Survival and response rates were analyzed according to the mutational status. 64 patients (48.1%) were available for mutational analysis in the chemotherapy alone group and 61 (45.1%) in the chemotherapy plus erlotinib group. RESULTS. 1.6% (2/116) harboured an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harboured a KRAS mutation (12 patients; exon 2), and 9.6% (12/118) a PIK3CA mutation (10 patients; exon 9 and 2 patients; exon 20). The addition of erlotinib to GEMOX in patients with KRAS wild type disease (n = 109) resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs. 12.5%, P = 0.024). In 95 patients with both wild type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to response rate (RR) as compared with GEMOX alone (P = 0.04). CONCLUSION. This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in biliary tract cancers (BTCs). Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild type BTCs. Keywords: KRAS, PIK3CA, Erlotinib Citation Format: Seung T. Kim, Joon Park. Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tract cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 578. doi:10.1158/1538-7445.AM2015-578