The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.

<h4>Background</h4>Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which m...

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Autores principales:	Justin Stebbing, Rachel Payne, Justine Reise, Adam E Frampton, Miranda Avery, Laura Woodley, Angelo Di Leo, Marta Pestrin, Jonathan Krell, R Charles Coombes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/044b6b7c00554788be15b9c372cae906
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spelling	oai:doaj.org-article:044b6b7c00554788be15b9c372cae9062021-11-18T07:46:41ZThe efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.1932-620310.1371/journal.pone.0062543https://doaj.org/article/044b6b7c00554788be15b9c372cae9062013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23667487/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.<h4>Patients and methods</h4>Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.<h4>Results</h4>There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43%) individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.<h4>Conclusions</h4>This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.<h4>Trial registration</h4>Clinical trials.gov NCT00820924.Justin StebbingRachel PayneJustine ReiseAdam E FramptonMiranda AveryLaura WoodleyAngelo Di LeoMarta PestrinJonathan KrellR Charles CoombesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62543 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Justin Stebbing Rachel Payne Justine Reise Adam E Frampton Miranda Avery Laura Woodley Angelo Di Leo Marta Pestrin Jonathan Krell R Charles Coombes The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
description	<h4>Background</h4>Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.<h4>Patients and methods</h4>Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.<h4>Results</h4>There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43%) individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.<h4>Conclusions</h4>This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.<h4>Trial registration</h4>Clinical trials.gov NCT00820924.
format	article
author	Justin Stebbing Rachel Payne Justine Reise Adam E Frampton Miranda Avery Laura Woodley Angelo Di Leo Marta Pestrin Jonathan Krell R Charles Coombes
author_facet	Justin Stebbing Rachel Payne Justine Reise Adam E Frampton Miranda Avery Laura Woodley Angelo Di Leo Marta Pestrin Jonathan Krell R Charles Coombes
author_sort	Justin Stebbing
title	The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
title_short	The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
title_full	The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
title_fullStr	The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
title_full_unstemmed	The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.
title_sort	efficacy of lapatinib in metastatic breast cancer with her2 non-amplified primary tumors and egfr positive circulating tumor cells: a proof-of-concept study.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/044b6b7c00554788be15b9c372cae906
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The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.

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