Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay

// Maria Schwaederle 1 , Hatim Husain 1 , Paul T. Fanta 1 , David E. Piccioni 1 , Santosh Kesari 1 , Richard B. Schwab 1 , Kimberly C. Banks 2 , Richard B. Lanman 2 , AmirAli Talasaz 2 , Barbara A. Parker 1 , Razelle Kurzrock 1 1 Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA 2 Guardant Health, Inc., Redwood City, CA, USA Correspondence to: Maria Schwaederle, e-mail: mschwaederle@ucsd.edu Keywords: cancer, liquid biopsy, ctDNA, actionable alteration, personalized therapy Received: September 30, 2015     Accepted: January 23, 2016     Published: February 01, 2016 ABSTRACT Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes ( EGFR , ERBB2 and MET )). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration ( TP53 ). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent.