Limited Efficacy of Anti-EGFR Monoclonal Antibodies in Colorectal Cancer Patients with Rare RAS Variants: Analysis of the C-CAT Database

Limited Efficacy of Anti-EGFR Monoclonal Antibodies in Colorectal Cancer Patients with Rare RAS Variants: Analysis of the C-CAT Database

Epidermal growth factor receptor (EGFR) inhibition is crucial in treating RAS wild-type metastatic colorectal cancer, yet current testing methods may miss rare RAS variants affecting treatment efficacy. We analyzed 4122 colorectal cancer patients receiving anti-EGFR antibodies from the Center for Ca...

Full description

Saved in:
Bibliographic Details
Main Authors: Shuhei Suzuki, Yosuke Saito, Koki Saito, Yuta Yamada, Koshi Takahashi, Ryosuke Kumanishi, Tadahisa Fukui, Takashi Yoshioka
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Current Issues in Molecular Biology
Subjects:
colorectal cancer
rare variants
<i>KRAS</i>
<i>NRAS</i>
genomic testing
cetuximab
Online Access:https://www.mdpi.com/1467-3045/46/12/869
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Epidermal growth factor receptor (EGFR) inhibition is crucial in treating RAS wild-type metastatic colorectal cancer, yet current testing methods may miss rare RAS variants affecting treatment efficacy. We analyzed 4122 colorectal cancer patients receiving anti-EGFR antibodies from the Center for Cancer Genomics and Advanced Therapeutics database, identifying 54 patients (1.3%) with rare RAS variants undetectable by standard testing. These patients showed significantly lower response rates to anti-EGFR therapy (28.3%) compared to RAS wild-type cases (44.6%, <i>p</i> = 0.003). Disease control rates were also lower in rare variant cases (60.9%) versus wild-type cases (80.0%). Most common rare variants included <i>KRAS</i> Q22K, A59E, and A11_G12insGA. Comprehensive genomic profiling revealed additional alterations in <i>TP53</i> (90.7%), <i>APC</i> (87.0%), and non-V600E <i>BRAF</i> mutations (25.9%). Our findings suggest that rare RAS variants predict poor anti-EGFR therapy response, highlighting the potential benefit of comprehensive genomic profiling before treatment initiation. This study provides real-world evidence supporting the clinical relevance of rare RAS variants in treatment decision-making for colorectal cancer. Future studies should focus on developing cost-effective comprehensive testing strategies and evaluating alternative treatment approaches for patients with rare RAS variants.
ISSN:1467-3037
1467-3045

Similar Items