Determining relevant biomarkers from tissue and serum that may predict response to single agent lapatinib in trastuzumab refractory metastatic breast cancer

Blackwell, Kimberley; Burstein, Harold J.; Pegram, Mark D.; Storniolo, A. M.; Salazar, Vanessa; Maleski, Janet; Lin, Xiwu; Spector, Neil L.; Stein, Steven; Berger, Mark S.

doi:10.1200/jco.2005.23.16_suppl.3004

Cited by 53 publications

(31 citation statements)

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“…21,22 In a phase III study evaluating capecitabine versus capecitabine plus lapatinib in women with metastatic disease, the addition of lapatinib led to a statistically significant improvement in TTP, and numerically fewer patients experienced CNS progression. 23 Given these data, and past data demonstrating improvements in response rate when cytotoxic agents are added to trastuzumab (compared with trastuzumab monotherapy), future studies of lapatinib for CNS disease should include an evaluation of lapatinib combined with cytotoxic agents with the potential to cross the blood-tumor barrier.…”

Section: Discussionmentioning

confidence: 99%

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Lin

Carey

Liu

et al. 2008

JCO

428

251

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Purpose-One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTAlthough all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. Results-Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). Patients and Methods-Patients Conclusion-The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.

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Section: Discussionmentioning

confidence: 99%

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Lin

Carey

Liu

et al. 2008

JCO

428

251

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“…Burstein et al 40 found no correlation between HER1 expression level assessed via IHC and response to lapatinib (six patients had an objective response to lapatinib by investigators review, two by independent review). Combined biomarker analysis was performed by Blackwell et al 90 in two large phase II studies with refractory MBC and they published initial data suggesting that expression levels of estrogen, progesterone and HER1 receptors may be related to lapatinib response in trastuzumab pretreated patients. Tumor tissues were obtained from each patient from the time of most recent biopsy.…”

Section: The Her Familymentioning

confidence: 99%

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

Bouchalová¹,

Cizkova²,

Cwiertka³

et al. 2010

BIOMED PAP

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Background. Breast cancer treatment trends are currently based on tailored therapies using tumor and patient biomarkers. Lapatinib is the first dual inhibitor of HER1 (EGFR, ErbB1) and HER2 (ErbB2, Neu) tyrosine kinases to be used in clinical practice. However, only HER2 is currently used for therapy indications and new predictors for the treatment with lapatinib are sought.Methods and results. This minireview focuses on lapatinib and its role in breast cancer treatment. Preclinical and clinical studies as well as pharmacological characteristics are briefly reviewed while the focus is on efficacy assessment including predictive factors for therapy outcome.Conclusion. Lapatinib (Tykerb/Tyverb) was Food and Drug Administration (FDA) approved in 2007 for use in combination with capecitabine for the treatment of HER2-positive advanced or metastatic breast cancer in patients who had received previous treatment (including anthracycline, taxane and trastuzumab containing regimens) and in 2010 for use in combination with letrozole for postmenopausal women with hormonal receptor positive and HER2-positive metastatic breast cancer. In contrast to trastuzumab (Herceptin), lapatinib is orally administered and it targets both HER2 and HER1 receptors. As a synthetic and oral tyrosine kinase inhibitor (TKI), it is convenient, cheaper and easier to produce than monoclonal antibodies. The recommended dosage is not dependent on body weight either. Lapatinib plasma level measurement could be an approach to tailored therapy for further optimizing the dose and prolonging this efficient therapy. New lapatinib response predictors are being evaluated. At this time, only HER2

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“…Biomarker analysis has also been conducted on biopsy samples taken from two large phase II studies in metastatic breast cancer patients treated with lapatinib and trastuzumabcontaining regimens (Blackwell et al 2005 Antitumor activity with lapatinib 900-1800 mg/day was reported in a meeting abstract of a phase I Japanese study in patients with advanced solid tumors (Minami et al 2004). Of the two patients who had partial responses, one recipient of lapatinib 1600 mg/day had trastuzumab-resistant breast cancer overexpressing ErbB2 and negative for ER and PR expression.…”

Section: Monotherapymentioning

confidence: 99%

Lapatinib: the evidence for its therapeutic value in metastatic breast cancer

Thomson¹

2005

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Determining relevant biomarkers from tissue and serum that may predict response to single agent lapatinib in trastuzumab refractory metastatic breast cancer

Cited by 53 publications

References 0 publications

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

Lapatinib: the evidence for its therapeutic value in metastatic breast cancer

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