722P - Molecular subgroup analysis of clinical outcomes in a phase 3 study of gemcitabine and oxaliplatin with or without erlotinib in advanced biliary tr...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Hepatobiliary Cancers
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Seung Kim
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors S. Kim1, H. Kim1, J. Lee2, S.H. Park3, Y.S. Park1, H.Y. Lim4, W. Kang5, J.O. Park5
  • 1Internal Medicine, Samsung Medical Center, 135-710 - Seoul/KR
  • 2Medicine, Samsung Medical Center, 135-710 - Seoul/KR
  • 3Internal Medicine, Sam Sung Medical Center, Seoul/KR
  • 4Department Of Medicine, Samsung Medical Center, Seoul/KR
  • 5Department Of Internal Medicine, Hematology, Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, seoul/KR



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 tumor specimens available for analysis was undertaken.


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. 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).


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.


All authors have declared no conflicts of interest.