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.

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 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.
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.
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.
Clinical trials.gov NCT00820924.
AuthorsJustin Stebbing, Rachel Payne, Justine Reise, Adam E Frampton, Miranda Avery, Laura Woodley, Angelo Di Leo, Marta Pestrin, Jonathan Krell, R Charles Coombes
JournalPloS one (PLoS One) Vol. 8 Issue 5 Pg. e62543 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23667487 (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
  • Receptor, Epidermal Growth Factor
  • Receptor, ErbB-2
  • Adult
  • Aged
  • Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
  • Gene Amplification
  • Humans
  • Middle Aged
  • Neoplastic Cells, Circulating (drug effects, pathology)
  • Quinazolines (pharmacology, therapeutic use)
  • Receptor, Epidermal Growth Factor (metabolism)
  • Receptor, ErbB-2 (genetics)

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