Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract Cancer.

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 (BTCs). Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken.

METHODS: Epidermal growth factor receptor (EGFR), KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp reactions. Survival and response rates (RRs) were analyzed according to the mutational status. Sixty-four 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) harbored an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harbored a KRAS mutation (12 patients; exon 2), and 9.6% (12/118) harbored 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 = .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 RR as compared with GEMOX alone (P = .04).

CONCLUSION: This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs.