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Ann Oncol. 2015 May;26(5):943-9. doi: 10.1093/annonc/mdv035. Epub 2015 Jan 28.

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

Author information

1
Division of Hematology and Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan.
2
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.
3
National Institute of Cancer Research, National Health Research Institutes, Tainan Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.
4
Division of Hematology and Oncology, Department of Internal Medicine, Tainan Municipal Hospital, Tainan.
5
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli.
6
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli.
7
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung.
8
Taipei Cancer Center, Taipei Medical University Hospital, Taipei.
9
Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, Taipei.
10
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan.
11
Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi.
12
Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung.
13
Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung.
14
Division of Hematology and Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung.
15
Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei.
16
National Institute of Cancer Research, National Health Research Institutes, Tainan Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan.
17
Department of Surgery, National Cheng Kung University Hospital, Tainan.
18
Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
19
National Institute of Cancer Research, National Health Research Institutes, Tainan Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung leochen@nhri.org.tw.

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

PMID:
25632066
DOI:
10.1093/annonc/mdv035
[Indexed for MEDLINE]

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