Journal of the Anus, Rectum and Colon
Online ISSN : 2432-3853
ISSN-L : 2432-3853
Trial Protocols
A Trial Protocol of Precision Medicine for Patients with RAS Wild Metastatic Colorectal Cancer Using Liquid Biopsy (RAS-liquid Study): A Prospective, Multicenter Observational Study
Akihisa MatsudaTakeshi YamadaTakao TakahashiKeiji HirataTakeshi NagasakaKei IshimaruKazuhiro SakamotoKeiji KodaToshiaki IshikawaHideyuki IshidaKenji MatsudaHidekazu KuramochiYoichiro YoshidaHiromichi SonodaHiroshi Yoshida
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2022 Volume 6 Issue 1 Pages 52-57


Background: Anti-epidermal growth factor receptor (EGFR) therapy has been identified to prolong the survival of metastatic colorectal cancer (mCRC) patients without RAS mutations. However, its efficacy is not always consistent for these patients. Genomic profiles of primary tumors and metastases are not always concordant; thus, chemotherapeutic agents can alter the tumor molecular profile. This molecular heterogeneity may explain resistance to anti-EGFR therapy. Liquid biopsy using circulating tumor DNA (ctDNA) is a novel, non-invasive diagnostic tool that can accommodate this molecular heterogeneity, providing a comprehensive, real-time view of the molecular landscape. In this study, we evaluated the predictive value of genomic mutations in ctDNA for primary and acquired resistance to anti-EGFR therapy.

Methods/Design: This study is a prospective, multicenter, observational study of mCRC patients with wild-type tissue RAS treated with cytotoxic agents and anti-EGFR antibodies as first-line therapy. Genomic mutations, including RAS, BRAF, PIK3CA, and EGFR in ctDNA, are assessed via Droplet Digital PCR before starting chemotherapy and every 3 months thereafter until disease progression. The target sample size is estimated to be 100. The primary endpoint is the response rate in patients without RAS mutation in their blood sample before starting chemotherapy.

Discussion: This study will clarify the predictive value of baseline RAS mutation in ctDNA for responses to anti-EGFR therapy; the frequency of emerging RAS, BRAF, PIK3CA, and EGFR mutations in ctDNA; and the association with secondary resistance to anti-EGFR therapy in first-line therapy for wild-type tissue RAS mCRC patients.

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© 2022 The Japan Society of Coloproctology

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