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.

Abstract

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.

• Authors: Justin Stebbing, Rachel Payne, Justine Reise, Adam E Frampton, Miranda Avery, Laura Woodley, Angelo Di Leo, Marta Pestrin, Jonathan Krell, R Charles Coombes
• Journal: PloS one (PLoS One) Vol. 8 Issue 5 Pg. e62543 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23667487 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Quinazolines
• Lapatinib
• EGFR protein, human
• ERBB2 protein, human
• ErbB Receptors
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• ErbB Receptors (metabolism)
• Gene Amplification
• Humans
• Lapatinib
• Middle Aged
• Neoplastic Cells, Circulating (drug effects, pathology)
• Quinazolines (pharmacology, therapeutic use)
• Receptor, ErbB-2 (genetics)