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

Seung Tae Kim; Kee-Taek Jang; Jeeyun Lee; Heung-Moon Jang; Hye-Jin Choi; Hye-Lim Jang; Se Hoon Park; Young Suk Park; Ho Yeong Lim; Won Ki Kang; Joon Oh Park

doi:10.1016/j.tranon.2014.12.003

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

Transl Oncol. 2015 Feb;8(1):40-6. doi: 10.1016/j.tranon.2014.12.003.

Authors

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
² Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
³ Department of Internal Medicine, Division of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁴ Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
⁵ Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: oncopark@skku.edu.

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 (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.