A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer

J. S. Chen, C. Hsu, N. J. Chiang, C. S. Tsai, H. H. Tsou, S. F. Huang, L. Y. Bai, I. C. Chang, H. S. Shiah, C. L. Ho, C. J. Yen, K. D. Lee, C. F. Chiu, K. M. Rau, M. S. Yu, Y. Yang, R. K. Hsieh, J. Y. Chang, Y. S. Shan, Y. ChaoLi Tzong Chen, Yung Hsin Chin, Tsai Rong Chung, Wei Lan Yu, Mei Hua Lee, Ling Fang Lin, Pei Chyi Lin, Ya Ling Wu, Hui Ling Wang, Li Ju Lu, Shiang Yi Chen, Chih Chu Wu, Te Chih Wei

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Abstract

Background: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. Patients and methods: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1: 1 to receive GEMOX (800 mg/m2 gemcitabine and 85 mg/m2 oxaliplatin) or C-GEMOX (500 mg/m2 cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). Results: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P=0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P=0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. Conclusions: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status.

Original languageEnglish
Article numbermdv035
Pages (from-to)943-949
Number of pages7
JournalAnnals of Oncology
Volume26
Issue number5
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Biliary tract cancer
  • Cetuximab
  • Chemotherapy
  • KRAS mutation

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Chen, J. S., Hsu, C., Chiang, N. J., Tsai, C. S., Tsou, H. H., Huang, S. F., Bai, L. Y., Chang, I. C., Shiah, H. S., Ho, C. L., Yen, C. J., Lee, K. D., Chiu, C. F., Rau, K. M., Yu, M. S., Yang, Y., Hsieh, R. K., Chang, J. Y., Shan, Y. S., ... Wei, T. C. (2015). A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer. Annals of Oncology, 26(5), 943-949. [mdv035]. https://doi.org/10.1093/annonc/mdv035