Genomic alterations in 670 patients with diverse cancers analyzed by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA)

11593 Background: NGS of blood-derived ctDNA allows non-invasive tumor profiling. Liquid biopsy studies with clinical correlation have so far been mainly limited to small size cohorts. Methods: We performed comprehensive plasma genomic testing of ctDNA (NGS) in 670 patients (pts) (54-70 genes); Guardant Health, Inc.; (Clinical Laboratory Improvement Amendment certified and College of American Pathologists accredited). Results: The most represented cancers were gastrointestinal (31.8%), brain (22.7%), and lung (20.7%) (Table). Sixty-three percent of pts (N = 423) had ≥1 alteration. The most frequent alterations (characterized and variants of unknown significance (VUSs)) were in TP53 (32.5% of pts), followed by EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, the breakdown was 30.7% ( TP53), 7.6% ( EGFR), 12.2% ( KRAS), and 7.7% ( PIK3CA). Interestingly, 32% of brain tumors had ≥1 ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations (P=0.019). Forty-eight percent of pts (320/670) had potentially actionable alterations; in 241, (75% of 320), by an FDA-approved drug (mostly off label). Illustrative examples of clinical utility will be presented such as a patient with gastric cancer and EGFRamplification in ctDNA who received anti-EGFR treatment (60% regression), as well a patient with aggressive gynecologic malignancy who received immunotherapy based on a hypermutated ctDNA profile. Conclusions: Most pts, including a subset of those with brain tumors, demonstrated ctDNA alterations. Pts with head and neck tumors harbored higher numbers of alterations. Overall, three quarters of pts with alteration(s) had ≥1 aberration that could potentially be pharmacologically tractable, suggesting the need to further assess the utility of ctDNA in a therapeutic setting. [Table: see text]