Details

Autor(en) / Beteiligte

• Siravegna, Giulia
• Sartore-Bianchi, Andrea
• Nagy, Rebecca J
• Raghav, Kanwal
• Odegaard, Justin I
• Lanman, Richard B
• Trusolino, Livio
• Marsoni, Silvia
• Siena, Salvatore
• Bardelli, Alberto

Titel

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

Ist Teil von

• Clinical cancer research, 2019-05, Vol.25 (10), p.3046-3053

Ort / Verlag

United States

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

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