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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.

AbstractBACKGROUND:
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.
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
Topics
  • 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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