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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.

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.

SUBMITTER: Stebbing J

PROVIDER: S-EPMC3647066 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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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.

Stebbing Justin J Payne Rachel R Reise Justine J Frampton Adam E AE Avery Miranda M Woodley Laura L Di Leo Angelo A Pestrin Marta M Krell Jonathan J Coombes R Charles RC

PloS one 20130507 5

<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 wa ...[more]

PMID: 23667487

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Project description:The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor-positive (hr+), human epidermal growth factor receptor 2-positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives.A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib-letrozole, letrozole, anastrozole, or trastuzumab-anastrozole as first-line treatment. Clinical inputs for lapatinib-letrozole and letrozole were taken from the EGF30008 trial (NCT00073528). Clinical inputs for anastrozole and trastuzumab-anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer's price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan's Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters.Quality-adjusted life years gained with lapatinib-letrozole were 0.236 compared with trastuzumab-anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib-letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab-anastrozole. Results from the societal perspective were similar.In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib-letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab-anastrozole.

Dataset Information

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.

Publications

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.

Similar Datasets

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