Plasma HER2 (ERBB2) Copy Number Predicts Response to HER2-targeted Therapy in Metastatic Colorectal Cancer.

摘要: Purpose: ERBB2 (HER2) amplification is an emerging biomarker in colon cancer, conferring sensitivity to combination anti-HER2 therapy. Measurement of HER2 copy number typically performed using surgical specimens, but cell-free circulating tumor DNA (ctDNA) analysis may be a noninvasive alternative. We determined the plasma (pCN) for detecting amplifications and whether pCN correlated with tissue-detected number. also assessed response HER2-targeted therapy based on suggest threshold predictive response. Experimental Design: Forty-eight pretreatment progression samples from 29 HER2-positive patients HERACLES A clinical trial were tested Guardant360 cfDNA assay. ERRB2 progression-free survival (PFS) best objective (BOR) applied adjustment method shedding maximum mutant allele fraction as surrogate content accurately determine Results: Forty-seven 48 had detectable ctDNA, 46 47 ERBB2-amplified basis [2.55–122 copies; 97.9% (95% confidence interval, 87.2%–99.8%)]. An adjusted ≥25.82 copies BOR PFS (P = 0.0347). Conclusions: viable alternative tissue-based genotyping metastatic setting. The platform utilized correctly identified 28 (96.6%) predicted benefit In this study, observed 2.4 25.82 are proposed select who will