Dynamic monitoring of HER2 amplification in circulating DNA of patients with metastatic colorectal cancer treated with cetuximab

• DOI: 10.1007/s12094-019-02215-7
• Publication Date: 2019-10-01T00:29:46Z
• Authors: R. Liu; X. Zhao; W. Guo; M. Huang; L. Qiu; W. Zhang; Z. Zhang; W. Li; X. Zhu; Z. Chen
• Keywords: Adult; Male; Receptor, ErbB-2; Gene Amplification; Cetuximab; Middle Aged; 3. Good health; 03 medical and health sciences; Antineoplastic Agents, Immunological; Treatment Outcome; 0302 clinical medicine; Drug Resistance, Neoplasm; Biomarkers, Tumor; Disease Progression; Humans; Female; Prospective Studies; Colorectal Neoplasms; Cell-Free Nucleic Acids; Aged

Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance.We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018.Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909).Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.