Abstract 3411: A pilot feasibility study to evaluate the efficacy of lapatinib in the elimination of HER2-positive circulating tumor cells in peripheral blood of women with metastatic breast cancer

Autor: Galaktia Kallergi, Harris Markomanolaki, Sofia Agelaki, Antonia Kalykaki, Dimitrios Mavroudis, Konstantinos Kalbakis, Vassilis Georgoulias
Rok vydání: 2012
Předmět:
Zdroj: Cancer Research. 72:3411-3411
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2012-3411
Popis: Background: The monitoring of circulating tumor cells (CTCs) detected in peripheral blood (PB) of patients (pts) with metastatic breast cancer (BC) has been proven a potent prognostic tool. CTCs detected after the completion of therapy are theoretically chemo- and/or hormone-resistant and could lead to disease progression. EGFR and HER2 expression has been demonstrated in CTCs from pts with BC. In the present trial we aimed to evaluate the efficacy of lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, in eliminating HER2 positive (+) CTCs of women with metastatic BC. Pts and methods: Pts with metastatic BC and HER2+ CTCs detected despite disease stabilization or response after the completion of prior therapy were eligible. Pts received lapatinib, 1500 mg/day orally till disease or CTC progression, whichever occurred first. HER2 expression was evaluated in cytospins of peripheral blood mononuclear cells’ (PBMCs) prepared from PB obtained at baseline and monthly thereafter. Cytospins were stained with HER2 along with cytokeratin antibody; a total of 10^6 PBMCs/pt were analyzed by double immunofluorescence. Results: Nineteen pts were enrolled from September 2008 to October 2011. Median age was 62 years, 12 (63.2%) pts were post-menopausal and 2 had HER2+ tumors. Twelve (63.2%) pts had visceral disease and 7 (36.8%) had received β3 lines of treatment. One pt discontinued treatment prior to the completion of the first cycle due to toxicity and 2 pts are not evaluable yet. The median duration of treatment was 4.0 (range, 0.5 - 34.0) months (mo). CTC counts declined in 15 out of 16 pts during treatment with a maximum percentage of decrease of 100% in all of them. The median time to and the median duration of nadir CTC counts were 1 mo (range, 1 - 3 mo) and 1 mo (range, 0 - 7 mo), respectively. Prior to the second treatment cycle, a decrease in CTC counts was observed in 14 (88%) pts, in 1 (7%) the CTC count increased by 33% and in 1 (7%) remained stable. Median percentage of CTC count decrease per pt was 100% (range, 45-100%). At baseline, a total of 2642 HER2+ CTCs were detected (median: 79/pt, range 2 - 617), whereas after the completion of first cycle a total of 430 HER2+ CTCs were identified (median: 0, range 0 - 223). Disease evaluation revealed stable disease in 5 pts and progressive disease in 11. In pts with stable disease a sustained decrease in CTC counts over 2 to 7 mo was observed. On the contrary, in 9 out of 11 pts with disease progression, the decrease in CTC counts was short-lasting (median 1.0 mo, range 0 - 4). Conclusions: Lapatinib is effective in decreasing HER2+ CTCs in pts with metastatic BC, irrespective of the HER2 status of the primary tumor. Sustained CTC reduction was associated with disease stabilization. The above results suggest that tailoring therapy according to targets present on CTCs could be an effective therapeutic strategy in BC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3411. doi:1538-7445.AM2012-3411
Databáze: OpenAIRE
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