Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival

Osumi,Hiroki; Shinozaki,Eiji; Osako,Masahiko; Kawazoe,Yoshimasa; Oba,Masaru; Misaka,Takaharu; Goto,Takashi; Kamo,Hitomi; Suenaga,Mitsukuni; Kumekawa,Yosuke; Ogura,Mariko; Ozaka,Masato; Matsusaka,Satoshi; Chin,Keisho; Hatake,Kiyohiko; Mizunuma,Nobuyuki

doi:10.3892/mco.2015.602

September-2015 Volume 3 Issue 5

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September-2015 Volume 3 Issue 5

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Article

Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival

Authors:
- Hiroki Osumi
- Eiji Shinozaki
- Masahiko Osako
- Yoshimasa Kawazoe
- Masaru Oba
- Takaharu Misaka
- Takashi Goto
- Hitomi Kamo
- Mitsukuni Suenaga
- Yosuke Kumekawa
- Mariko Ogura
- Masato Ozaka
- Satoshi Matsusaka
- Keisho Chin
- Kiyohiko Hatake
- Nobuyuki Mizunuma
View Affiliations / Copyright

Affiliations: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Department of Surgery, Kagoshima Medical Association Hospital, Kagoshima, Kagoshima, Japan, Department of Medical Informatics and Economics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, Department of Gastroenterology, Kirishima Medical Center, Kirishima, Kagoshima, Japan, Department of Surgery, Koga General Hospital, Miyazaki, Japan, Department of Medical Oncology and Hematology, New Drug Development Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Pages: 1053-1057
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Published online on: July 9, 2015

https://doi.org/10.3892/mco.2015.602
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Abstract

A number of previous studies have reported that 30-50% of patients with colorectal cancer (CRC) harbor Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which is a major predictive biomarker of resistance to epidermal growth factor (EGFR)‑targeted therapy. Treatment with an anti-EGFR inhibitor is recommended for patients with KRAS wild-type metastatic colorectal cancer (mCRC). A recent retrospective study of cetuximab reported that patients with KRAS p.G13D mutations had better outcomes compared with those with other mutations. The aim of this retrospective study was to assess the prevalence of KRAS p.G13D mutations and evaluate the effectiveness of cetuximab in mCRC patients with KRAS p.G13D or other KRAS mutations. We reviewed the clinical records of 98 mCRC patients with KRAS mutations who were treated between August, 2004 and January, 2011 in four hospitals located in Tokyo and Kyushu Island. We also investigated KRAS mutation subtypes and patient characteristics. In the patients who received cetuximab, univariate and multivariate analyses were performed to assess the effect of KRAS p.G13D mutations on progression-free survival (PFS) and overall survival (OS). Of the 98 patients, 23 (23.5%) had KRAS p.G13D-mutated tumors, whereas 75 (76.5%) had tumors harboring other mutations. Of the 31 patients who received cetuximab, 9 (29.0%) had KRAS p.G13D mutations and 22 (71.0%) had other mutations. There were no significant differences in age, gender, primary site, pathological type, history of chemotherapy, or the combined use of irinotecan between either of the patient subgroups. The univariate analysis revealed no significant difference in PFS or OS between the patients with KRAS p.G13D mutations and those with other mutations (median PFS, 4.5 vs. 2.8 months, respectively; P=0.65; and median OS, 15.3 vs. 8.9 months, respectively; P=0.51). However, the multivariate analysis revealed a trend toward better PFS among patients harboring p.G13D mutations (PFS: HR=0.29; 95% CI: 0.08‑1.10; P=0.07; OS: HR=0.23; 95% CI: 0.04-1.54; P=0.13). In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p.G13D mutation, compared with those harboring other mutations. However, further investigation is required to clearly determine the benefits of cetuximab treatment in patients with KRAS p.G13D mutation-positive mCRC.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival

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