The Efficacy of Lapatinib in Metastatic Breast Cancer with HER2 Non-Amplified Primary Tumors and EGFR Positive Circulating Tumor Cells: A Proof-Of-Concept StudyReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

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.

Patients and Methods

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.

Results

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.

Conclusions

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.

Trial Registration

Clinical trials.gov NCT00820924



Autor: Justin Stebbing , Rachel Payne, Justine Reise, Adam E. Frampton, Miranda Avery, Laura Woodley, Angelo Di Leo, Marta Pestrin, Jona

Fuente: http://plos.srce.hr/



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