Abstract 374P
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.
Clinical trial identification
Editorial acknowledgement
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.
Resources from the same session
64P - Entrectinib in locally advanced/metastatic ROS1 and NTRK fusion-positive non-small cell lung cancer (NSCLC): Updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Filippo de Braud
Session: Poster display session
Resources:
Abstract
65P - Updated efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Christian Rolfo
Session: Poster display session
Resources:
Abstract
66P - Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
Presenter: Matthew Krebs
Session: Poster display session
Resources:
Abstract
67P - Pooled safety analysis of tepotinib in Asian patients with advanced solid tumours
Presenter: Kentaro Yamazaki
Session: Poster display session
Resources:
Abstract
68P - A novel anti-EGFR antibody HLX07 for potential treatment of squamous cell carcinoma of the head and neck
Presenter: Ming Mo Hou
Session: Poster display session
Resources:
Abstract
69P - Irinotecan and cisplatin therapy-induced neutropenia as a prognostic factor in patients with extensive-disease small cell lung cancer
Presenter: Hiroshi Ishikawa
Session: Poster display session
Resources:
Abstract
70P - Is safe and efficient by intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for cholecystolithiasis combined with common bile duct stones: A meta-analysis
Presenter: Jiasheng Cao
Session: Poster display session
Resources:
Abstract
71P - Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer: A propensity score analysis
Presenter: Chaobin He
Session: Poster display session
Resources:
Abstract
72P - Novel technique of near-focus mode for accurate operation during endoscopic submucosal tunneling procedure: A two-center comparative study
Presenter: Wei Peng
Session: Poster display session
Resources:
Abstract
73P - Cabozantinib in combination with anti-PD1 immune checkpoint inhibitor in syngeneic tumour mouse models
Presenter: Rachel Sparks
Session: Poster display session
Resources:
Abstract