KRAS mutations detected by the amplification refractory mutation system-Scorpion assays strongly correlate with therapeutic effect of cetuximab
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Updated: May 31, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
H Bando1, T Yoshino, K Tsuchihara
1Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
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.
Insights
Sensitive KRAS testing, using the amplification refractory mutation system-Scorpion assay (ARMS/S), improves treatment decisions for anti-EGFR therapies compared to direct sequencing. ARMS/S identified more KRAS mutations, leading to better patient outcomes.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- KRAS mutation testing is crucial for guiding anti-epidermal growth factor antibody therapy in cancer treatment.
- Direct sequencing is a standard method for KRAS testing, but its sensitivity may be limited.
- The amplification refractory mutation system-Scorpion assay (ARMS/S) offers a more sensitive approach to KRAS mutation detection.
Purpose of the Study:
- To compare the diagnostic accuracy of sensitive KRAS testing (ARMS/S) with direct sequencing.
- To evaluate the impact of ARMS/S-based KRAS testing on clinical treatment decisions and patient outcomes.
- To assess the predictive value of ARMS/S for anti-EGFR antibody efficacy.
Main Methods:
- Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor specimens.
- KRAS mutation status was determined using both direct sequencing and the ARMS/S assay.
- Patients identified as wild-type (WT) KRAS by direct sequencing received cetuximab; treatment efficacy was assessed based on ARMS/S results.
Main Results:
- The ARMS/S assay detected a higher overall KRAS mutation rate (44.0%) compared to direct sequencing (37.0%).
- Among patients treated with cetuximab based on direct sequencing WT status, those identified as WT by ARMS/S showed a 16.0% response rate, while ARMS/S mutant patients did not respond.
- ARMS/S identified WT patients demonstrated significantly improved progression-free survival (PFS) and overall survival (OS) compared to ARMS/S mutant patients.
Conclusions:
- Sensitive KRAS testing with ARMS/S provides enhanced predictive accuracy for anti-EGFR antibody efficacy.
- ARMS/S testing may improve patient selection for targeted therapies, leading to better clinical outcomes.
- Quality-controlled, sensitive KRAS testing is essential for optimizing treatment strategies in oncology.
