Phase II trial of cetuximab plus irinotecan for oxaliplatin- and irinotecan-based chemotherapy-refractory patients with advanced and/or metastatic colorectal cancer: evaluation of efficacy and safety based on KRAS mutation status (T-CORE0801)

Hiroshi Soeda; Hideki Shimodaira; Makio Gamoh; Hideaki Ando; Hideki Isobe; Takeshi Suto; Shin Takahashi; Yuichi Kakudo; Kenji Amagai; Takahiro Mori; Mika Watanabe; Takuhiro Yamaguchi; Shunsuke Kato; Chikashi Ishioka

doi:10.1159/000360989

Phase II trial of cetuximab plus irinotecan for oxaliplatin- and irinotecan-based chemotherapy-refractory patients with advanced and/or metastatic colorectal cancer: evaluation of efficacy and safety based on KRAS mutation status (T-CORE0801)

Oncology. 2014;87(1):7-20. doi: 10.1159/000360989. Epub 2014 Jun 24.

Authors

Hiroshi Soeda¹, Hideki Shimodaira, Makio Gamoh, Hideaki Ando, Hideki Isobe, Takeshi Suto, Shin Takahashi, Yuichi Kakudo, Kenji Amagai, Takahiro Mori, Mika Watanabe, Takuhiro Yamaguchi, Shunsuke Kato, Chikashi Ishioka

Affiliation

¹ Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

PMID: 24968756
DOI: 10.1159/000360989

Abstract

Background: Mutations in the KRAS gene have been identified as negative predictors of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy by patients with metastatic colorectal cancer (mCRC). However, it has been based on the study of mainly Caucasian mCRC patients. This prospective study investigated the relationship between the mutation status of EGFR-related genes including KRAS and the response rate (RR) to cetuximab plus irinotecan therapy in Japanese mCRC patients.

Methods: Samples taken from 43 chemotherapy-refractory mCRC patients who had undergone cetuximab plus irinotecan therapy at 11 medical centers in Japan were subjected to direct DNA sequencing to determine the KRAS, BRAF, PIK3CA, NRAS, and AKT1 mutation status. The clinical outcome after the treatment was evaluated for each mutation status.

Results: KRAS mutations were detected in 31.7% of 41 eligible patients. The RR to cetuximab plus irinotecan therapy was found to be 17.9 and 0% in the KRAS wild-type and mutant subgroups, respectively.

Conclusion: Despite the identification of a lower-than-expected RR to treatment by the KRAS wild-type subgroup, KRAS mutation status appears to be a useful predictive marker of response to cetuximab plus irinotecan therapy in Japanese mCRC patients.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Camptothecin / administration & dosage
Camptothecin / analogs & derivatives
Cetuximab
Class I Phosphatidylinositol 3-Kinases
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / genetics
Colorectal Neoplasms / mortality
Colorectal Neoplasms / pathology
DNA Mutational Analysis
Disease-Free Survival
Female
GTP Phosphohydrolases / genetics
Humans
Irinotecan
Kaplan-Meier Estimate
Liver Neoplasms / drug therapy*
Liver Neoplasms / genetics
Liver Neoplasms / mortality
Liver Neoplasms / secondary
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / mortality
Lung Neoplasms / secondary
Male
Membrane Proteins / genetics
Middle Aged
Organoplatinum Compounds / administration & dosage
Oxaliplatin
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins p21(ras)
Treatment Outcome
ras Proteins / genetics

Substances

Antibodies, Monoclonal, Humanized
KRAS protein, human
Membrane Proteins
Organoplatinum Compounds
Proto-Oncogene Proteins
Oxaliplatin
Irinotecan
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
BRAF protein, human
Proto-Oncogene Proteins B-raf
GTP Phosphohydrolases
NRAS protein, human
Proto-Oncogene Proteins p21(ras)
ras Proteins
Cetuximab
Camptothecin