HER2 amplification is demonstrated to influence response to therapy and outcomes in metastatic colorectal cancer (mCRC), but its role in resectable CRC remains unclear.
This study investigated the prognostic impact of WES-defined ERBB2 amplification and its association with adjuvant chemotherapy (ACT) efficacy and circulating tumor DNA (ctDNA) in resectable CRC. Data from 3607 patients with resectable CRC from the GALAXY study were analyzed. HER2 amplification was defined using ERBB2 copy number alterations based on whole exome sequencing of tumor specimens. We analyzed disease-free survival (DFS) in WES-defined ERBB2 amplified CRC, evaluating ACT benefit and the correlation between ERBB2 copy number and ctDNA status.
No significant difference in DFS was observed between those with and without WES-defined ERBB2 amplification in a univariate (P = 0.0659) or a multivariate analysis (P = 0.2300). Among patients with pathological stage III, ACT was associated with improved DFS in the non-amplified subgroup (HR 0.67, P = 0.0002), particularly in the subgroup of patients with early post-operative (2-10 weeks following surgical resection) ctDNA-positivity (HR 0.27, P
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