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

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Giulia SiravegnaAlberto Bardelli

Abstract

ERBB2 (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 ERBB2 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 ERRB2 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 ERBB2-amplified on the basis of cfDNA [2.55-122 copies; 97.9% sensitivity (95% confidence interval, 87.2%-99.8%)]. An adjusted ERBB2 pCN of ≥25.82...Continue Reading

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Citations

Sep 5, 2019·Journal of Clinical Medicine·Ai Hironaka-MitsuhashiAkihiko Suto
Aug 13, 2020·Therapeutic Advances in Medical Oncology·Giulia MartiniElena Elez
May 7, 2020·Frontiers in Oncology·Shuhang WangNing Li
Aug 30, 2020·Biomedicines·Marco VacanteAntonio Biondi
Aug 25, 2020·ESMO Open·Yoshiaki Nakamura, Kohei Shitara
Nov 10, 2020·CA: a Cancer Journal for Clinicians·Michael L ChengGeoffrey R Oxnard
Apr 18, 2021·Nature Reviews. Clinical Oncology·Federica Di NicolantonioAlberto Bardelli
Apr 25, 2021·Nature Communications·Belinda KingstonNicholas C Turner
Jan 24, 2020·Gastroenterology·Rodrigo DienstmannUNKNOWN COLOSSUS Consortium
Jul 3, 2021·International Journal of Molecular Sciences·Chiara GuariniCamillo Porta
Jan 29, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G SiravegnaA Bardelli

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