SDPS-20 THE HER2 FLIP: HER2 AMPLIFICATION OF TUMOR CELLS IN THE CEREBROSPINAL FLUID (CSF-TCS) OF PATIENTS WITH LEPTOMENINGEAL METASTASIS HAVING SOLID TUMORS; IMPLICATIONS FOR TREATING THE LM TUMOR WITH ANTI-HER2 THERAPY

• Published in: Neuro-oncology advances Vol. 5; no. Supplement_3; p. iii20
• Main Authors: Kumthekar, Priya, Youssef, Michael, Blondin, Nicholas, Azadi, Amir, Piccioni, David, Glantz, Michael, Carillo, Jose, Avgeropoulos, Nicholas, Makar, Sherif, Blouw, Barbara, Natasha, Anna, Fisher, Deanna, Huynh, Lan, Peters, John, Sweed, Nathan, Dugan, Michael, Kesari, Santosh
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 04.08.2023
• Subjects: Final Category: Screening/Diagnostics/Prognostics
• ISSN: 2632-2498; 2632-2498
• DOI: 10.1093/noajnl/vdad070.077

Abstract INTRODUCTION Patients diagnosed with Leptomeningeal Metastasis (LM) have limited treatment options. However, they may benefit from targetable therapy. LM breast cancer patients with HER2 positive primary tumors treated with IT Trastuzumab experienced clinical benefit (Malani, 2020), and improved craniospinal PFS (Figura, 2019). HER2 amplification of the primary and metastatic tumors can be heterogeneous. Biocept’s CNSideTM is a CLIA validated Laboratory Developed Test and is used commercially at the discretion of Physicians to detect CSF tumor cells (CSF-TCs). We analyzed HER2 amplification on CSF-TCs in LM patients with breast-, upper GI cancer as well as Non-Small Cell Lung Cancer (NSCLC). METHODS CSF was collected from patients with suspected or confirmed LM having Breast Cancer (N=334 patients, N=181 evaluable), NSCLC (N=28 patients) or upper GI cancer (N=4 patients, N=2 evaluable). CSF TCs were tested for HER2 amplification by FISH using CNSide. RESULTS For the breast cancer patients, 38% (68/181) had HER2 FISH detected on CSF TCs, 60% (109/181) had a HER2 negative primary tumor of which 35% (38/109) had HER2 positive CSF-TCs. Furthermore, 8% (14/181) had an equivocal HER2 primary tumor, 21% (3/14) of which had HER2 positive CSF-TCs. For the NSCLC patients, 50% (14/28) showed HER2 amplification on the CSF-TCs. For the upper GI cancer patients, one patient had an equivocal HER2 primary tumor, and HER2 positive CSF-TCs. CONCLUSION HER2 amplification is detected on CSF-TCs of patients with LM having breast cancer, upper GI cancer or NSCLC cancer. For NSCLC patients, HER2 positivity in the LM can be associated with drug resistance. Patients who have a HER2 negative primary tumor can develop HER2 positive LM, allowing for an anti-HER2 targetable treatment. Additional studies are needed to establish the clinical utility of CNSide in the detection of HER2 on the CSF-TCs to direct treatment of anti-HER2 therapy in patients with LM.