KRAS Mutations Detected by the Amplification Refractory Mutation System-Scorpion Assays Strongly Correlate with Therapeutic Effect of Cetuximab

Overview

Journal Br J Cancer

Specialty Oncology

Date 2011 Jul 7

PMID 21730978

Citations 20

Authors

H Bando

T Yoshino

K Tsuchihara

N Ogasawara

N Fuse

T Kojima

M Tahara

M Kojima

K Kaneko

T Doi

A Ochiai

H Esumi

A Ohtsu

Affiliations

Soon will be listed here.

Abstract

Background: We aimed to compare the sensitive and quality-controlled KRAS testing with direct sequencing and to assess the impact on decision making of treatment.

Patients And Methods: We analysed genomic DNA isolated from macrodissected formalin-fixed paraffin-embedded specimens by direct sequencing and an amplification refractory mutation system-Scorpion assay (ARMS/S) method. Cetuximab was administered to patients identified as having wild-type (WT) KRAS using direct sequencing. Therapeutic effects were evaluated according to their KRAS status as determined by ARMS/S.

Results: Among the 159 patients, the overall mutation rate was determined to be 37.0% by direct sequencing and 44.0% by ARMS/S. For the patients diagnosed as WT by direct sequencing and treated with cetuximab (n=47), a response rate of 16.0% was observed for 38 ARMS/S WT patients, whereas 9 ARMS/S mutant (MUT) patients failed to respond. The ARMS/S WT patients showed significant improvement in progression-free survival (PFS) and overall survival (OS) compared with ARMS/S MUT patients (PFS median 5.0 vs 1.7 months, hazards ratio (HR)=0.29, P=0.001; OS median 12.1 vs 3.8 months, HR=0.26, P=0.001).

Conclusion: Sensitive and quality-controlled KRAS testing may provide improved predictive power to determine the efficacy of anti-epidermal growth factor antibodies.

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