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P05.10 Prospective evaluation of cerebrospinal fluid circulating tumor cells (CSF CTC) in patients with HER2 positive cancers and leptomeningeal metastases receiving treatment with intrathecal trastuzumab

ABSTRACT: Abstract Background The validated CellSearch system (Janssen Diagnostics, LLC), utilizing an immunomagnetic CTC selection method based on EPCAM antibody conjugated ferroparticles, is an FDA-approved methodology for enumerating CTC from blood in pts with breast, prostate and colon cancers. The CellSearch system has been used to evaluate CSF CTC of pts with leptomeningeal metastasis (LM) and has demonstrated potential as a diagnostic marker and response to cancer treatment. We explored the use of CSF CTC enumeration in the follow-up of pts with LM from HER2+ cancers receiving intrathecal (IT) therapy, aimed at characterizing changes over time as a potential biomarker of treatment response. Material and Methods CSF from pts participating in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was evaluated by CellSearch system. 3 ml CSF from a ventricular reservoir was collected for CSF CTC enumeration at pre-treatment Day 1 of each cycle and correlated with CSF cytology from the same sample, and with clinical and radiographic response. LM progression was defined as clinical or radiographic worsening. Results Fifteen patients with HER2+ LM (14 breast, 1 colon) were enrolled; 14 were women. Six patients had baseline positive CSF cytology; the remaining were diagnosed by MRI. Of the 15 patients, 10 had greater than 1 cycle of treatment to be evaluable; 5 patients progressed during cycle 1. Median CSF CTC at baseline was 22 per 3ml (range 0–200); 2 patients had no detectable CSF CTCs. A decrease in CSF CTC was observed in 5 patients after cycle 1 and remained low (mean =9.5, range 0–92) in 2 patients while disease was stable. 3 patients had a rise in CSF CTCs roughly 1 month prior to progression. In the 10 patients with HER2 analysis, number of CTCs correlated with HER 2 expression. Conclusion CSF CTC HER2 expression provided further affirmation that CTCs are malignant. Changes in CSF CTC enumeration allow quantitative surveillance of treatment response and should be further investigated.

SUBMITTER: Pentsova E

PROVIDER: S-EPMC6144227 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Project description:BackgroundPatients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.MethodsWe conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.Results7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.ConclusionsThe results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.

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P05.10 Prospective evaluation of cerebrospinal fluid circulating tumor cells (CSF CTC) in patients with HER2 positive cancers and leptomeningeal metastases receiving treatment with intrathecal trastuzumab

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