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
458P - Mutation tracking in circulating tumour DNA predicts relapse in completely resected EGFR-mutated NSCLC
Presenter: Martin Filipits
Session: Poster display session
Resources:
Abstract
460P - Mendelian randomization study showed no causality between metformin use and lung cancer risk
Presenter: Jiayi Shen
Session: Poster display session
Resources:
Abstract
461P - Blood trace minerals and lung cancer: A Mendelian randomization study
Presenter: Wei Xian
Session: Poster display session
Resources:
Abstract
463P - Prediction of invasiveness in lung adenocarcinoma using machine learning algorithm based on 3D-CT imaging
Presenter: Yusuke Saeki
Session: Poster display session
Resources:
Abstract
459P - Fish intake, dietary polyunsaturated fatty acids, and lung cancer: systematic review and dose-response meta-analysis of 1.7 million men and women
Presenter: Chao Cao
Session: Poster display session
Resources:
Abstract
462P - Usefulness for prevention of postoperative cerebrovascular complications in patients with lung cancer using carotid ultrasonography
Presenter: Sadanori Takeo
Session: Poster display session
Resources:
Abstract
468P - Histological type analysis of 10-year follow-up of WJTOG0105: A phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer
Presenter: Masahiro Tsuboi
Session: Poster display session
Resources:
Abstract
469P - Comparison of combined chemoradiotherapy regimens; Paclitaxel plus carboplatin and cisplatin plus etoposide for locally advanced non-small cell lung cancer: A randomised phase III trial
Presenter: Alper Ata
Session: Poster display session
Resources:
Abstract
472P - Integration of expression rate and absolute cell counts of PD-1+ stromal tumour-infiltrating lymphocytes: Prognostic significance in esophageal squamous cell carcinoma
Presenter: Qingkun Song
Session: Poster display session
Resources:
Abstract
467P - The free-circulating mtDNA copies number in plasma of patients with NSCLC
Presenter: Olga Bulgakova
Session: Poster display session
Resources:
Abstract