Abstract 1521P
Background
Epithelioid hemangioendothelioma (EHE) and liver angiosarcomas (LAS) are rare, malignant vascular sarcomas of the liver. LAS is frequently progressive and fatal as it is often detected in advanced stages. The clinical course of EHE exhibits a dual nature as it is often indolent but can grow rapidly and metastasize unpredictably. There is a dearth of effective targeted therapies in this disease space.
Methods
Comprehensive genomic profiling (CGP) was performed using the Foundation Medicine Inc. (FMI) database on 32 LAS and 14 EHE clinically advanced cases between 6/2013-12/2020 using a hybrid capture-based assay of up to 324 genes to detect genomic alterations (GA), tumor mutational burden (TMB) and microsatellite instability (MSI). PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC and scored using the tumor proportion score (TPS) method.
Results
Median age of both groups was similar (61 in LAS vs 60 in EHE). There was a slight male preponderance in the LAS group compared to the EHE group (56% vs 43%). The LAS group featured significantly more GA/tumor than EHE group (3.91vs 1.57 p<.0001). The cell cycle regulatory GA TP53 were significantly more frequent in the LAS group(59.4% vs 0% p=.002). CAMTA1 fusions were seen in all 14 cases of EHE. GA in other potentially targetable genes were uncommon in both groups but EHE cases featured slightly more GA in DNA damage and repair (DDR) pathways including BRCA1, FANCD2, ATM than LAS. Interestingly, ATRX mutations were more prevalent in LAS (29% vs 0% p=.04). GA in targetable kinases including EGFR, FGFR, ERBB2, ALK, and PIK3CA were not seen. GA in KRAS were observed in 9.4% of LAS cases. GA in NOTCH 1 and KIT were found in 6.3% and 3.1% of LAS, respectively. Overall TMB was low with very few cases having TMB ≥ 10 mutations/Mb. PD-L1 expression was relatively low in both groups.
Conclusions
CGP analysis of LAS and EHE in this observational study illustrates the heterogeneous nature of these cancers. Overall, the analysis showed that CAMTA1 fusions are pathognomonic for EHE. It also identified certain targetable GA in the cell cycle regulatory and DDR pathways. Our findings warrant further evaluation of clinically advanced LAS and EHE pts by CGP to potentially identify more targetable genomic pathways.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Shreenivas: Financial Interests, Personal and Institutional, Research Grant: Natera. R. Kurzrock: Financial Interests, Personal and Institutional, Research Grant: Biological Dynamics, Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech; Financial Interests, Personal, Ownership Interest, co founder and equity interest: CureMatch Inc; Financial Interests, Personal, Ownership Interest, equity interest: CureMetrix, IDbyDNA; Financial Interests, Personal, Other, consultant and/or speaker fees and/or advisory board: Actuate Therapeutics, Bicara Therapeutics, AstraZeneca, Pfizer, Neomed, Roche, X-Biotech. A. Clark: Financial Interests, Personal, Full or part-time Employment, full time employee of Foundation Medicine: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. K. dougherty: Financial Interests, Personal, Full or part-time Employment, Full-time employee (Medical Science Liaison) of Foundation Medicine, Inc.: Foundation Medicine, Inc.; Financial Interests, Personal, Stocks/Shares: Foundation Medicine, Inc., Myriad Genetics, Inc.; Non-Financial Interests, Institutional, Proprietary Information: Foundation Medicine, Inc.; Non-Financial Interests, Member: National Society of Genetic Counselors, American Society of Clinical Oncology; Other, Employee from January 2014- October 2020: Myriad Genetics, Inc. N.A. Danziger: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffman La-Roche LTd. S. Chakrabarti: Financial Interests, Personal, Invited Speaker, Speaker bureau: Natera Inc; Financial Interests, Personal, Other, Advisory role: QED THerapeutics. J. Charlson: Financial Interests, Personal, Other, Educational materials: Deciphera; Financial Interests, Personal, Advisory Board: Adaptimmune. J.S. Ross: Financial Interests, Personal, Full or part-time Employment, Medical Director: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holdings, Tango Therapeutics, Celsius Therapeutics. All other authors have declared no conflicts of interest.