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 Chao, L T Chen, Taiwan Cooperative Oncology Group, Wen-Chi Shen, Hung-Chih Hsu, Chih-Hung Hsu, Ying-Chun Shen, Tsang-En Wang, Chung-Pin Li, Ming-Huang Chen, Wei-Yao Kao, Ping-Ying Chang, Cheng-Chung Wu, Chien-Lin Teng, Chang-Hsien Lu, Shyh-Jer Lin, Being-Whey Wang, Yen-Yang 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, 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 Chao, L T Chen, Taiwan Cooperative Oncology Group, Wen-Chi Shen, Hung-Chih Hsu, Chih-Hung Hsu, Ying-Chun Shen, Tsang-En Wang, Chung-Pin Li, Ming-Huang Chen, Wei-Yao Kao, Ping-Ying Chang, Cheng-Chung Wu, Chien-Lin Teng, Chang-Hsien Lu, Shyh-Jer Lin, Being-Whey Wang, Yen-Yang 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
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/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) 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.
Clinical trials number: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.
Keywords: KRAS mutation; biliary tract cancer; cetuximab; chemotherapy.
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Source: PubMed