374PCirculating tumour DNA (ctDNA) identifies actionable genetic alterations in Middle Eastern and Asian (MEA) patients diagnosed with carcinoma of unknown primary (CUP)

Abstract Background The clinical work-up for CUP includes examination of biomarkers by serum chemistry and tissue immunohistochemistry. Comprehensive next-generation sequencing (NGS) of DNA has the potential to assess multiple target genes in a single test from genetic material isolated from tissue or blood (ctDNA). We explored the ability of the NGS assay Guardant360 to detect actionable biomarkers in ctDNA from MEA patients with CUP. Methods We identified all cases of Guardant360 ordered in MEA through 15 June 2019 for which the diagnosis of “carcinoma of unknown primary” was specified on the test requisition form. Actionable biomarkers were defined as alterations included in the Guardant360 panel and associated with a targeted therapy in any solid tumor as recommended by the National Comprehensive Cancer Network. Synonymous point mutations and variants of unknown significance were excluded. Results At the time of data cut-off, 90 tests were ordered for CUP. These included 47 from Israel, 14 from Japan, 11 from Hong Kong, 5 from Thailand, and 3 each from India, Singapore, and Vietnam. These came from 44 men and 46 women, with a median age of 66.5 years. Three tests were canceled prior to processing. ctDNA was identified in 75 of 87 samples (86.2% detection rate). Genes commonly mutated included TP53 (41 cases), KRAS (14), and NF1 (6). Actionable biomarkers were detected in 28/75 cases (37%), including EGFR (6 cases with actionable mutations plus 2 with exon 20 insertions), PIK3CA (5), KIT (4), ALK (4), ERBB2 (3), and BRCA2 (3). Nine cases (12%) had alterations in DNA damage response genes (ATM, BRCA1, BRCA2, MLH1), and 12 (16%) had alterations in genes involved in the PI3K signaling pathway (PIK3CA, PTEN, STK11). Conclusions Analysis of ctDNA from patients with advanced CUP reveals a significant number with actionable and potentially actionable genetic alterations. In some instances, the alteration (eg, EGFR mutation, ALK fusion) may suggest tissue of cancer origin. Therefore, comprehensive genetic profiling of tumor DNA should be considered in the work-up for patients with CUP. Legal entity responsible for the study Guardant Health AMEA. Funding Guardant Health AMEA. Disclosure N. Peled: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AID Genomics; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: NovellusDx; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (institution), Advisory / Consultancy: Guardant Health. S.M. Stemmer: Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Can-Fite BioPharma; Research grant / Funding (institution), Shareholder / Stockholder / Stock options: CTG Pharma; Shareholder / Stockholder / Stock options: DocBoxMD; Shareholder / Stockholder / Stock options: TyrNovo Ltd; Shareholder / Stockholder / Stock options: Vype; Advisory / Consultancy: Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BiolineRx; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): GEICAM; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Moderna Therapeutics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Rafael Pharmaceuticals; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Silenseed; Research grant / Funding (institution): Syncore; Research grant / Funding (institution): Teva; Research grant / Funding (institution): Tiziana Life Sciences. S. Olsen: Shareholder / Stockholder / Stock options: AstraZeneca; Shareholder / Stockholder / Stock options, Full / Part-time employment: Guardant Health. All other authors have declared no conflicts of interest.