Cardiac Safety of Lapatinib: Pooled Analysis of 3689 Patients Enrolled in Clinical Trials

Perez, Edith A.; Koehler, Maria; Byrne, Julie; Preston, A.; Rappold, Erica; Ewer, Michael S.

doi:10.1016/s0025-6196(11)60896-3

Cited by 282 publications

(116 citation statements)

References 20 publications

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“…The cardiac safety of anti-HER-2 therapy is likely to be agent specific, as the early clinical experience with Lapatinib, a dual tyrosine kinase inhibitor of the EGFR and HER-2 receptors, suggests that it may produce less cardiotoxicity compared with Trastuzumab. However, more studies are needed to better characterize the cardiac effects of Lapatinib, since the patient population studied was heterogeneous and highly selected, limiting the conclusions that can be drawn from this early data [26]. A new anti-ErbB2 monoclonal antibody which recognizes an epitope distant from that of Trastuzumab (in the extracellular portion of ErbB2), Pertuzumab, does not seem to be significantly cardiotoxic [11], but data are still very preliminary, since it is still being tested in pivotal clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors

Fedele

Riccio

Coppola

et al. 2011

Breast Cancer Res Treat

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Two novel human antitumor immunoconjugates, made up of a human anti-ErbB2 scFv, Erbicin, fused with either a human RNase or the Fc region of a human IgG1, are selectively cytotoxic for ErbB2-positive cancer cells in vitro and in vivo. The Erbicin-derived immunoagents (EDIA) target an epitope different from that of trastuzumab, the only humanized antibody currently prescribed for treatment of ErbB2-positive breast cancer (BC). As Trastuzumab has shown cardiotoxic effects, in this study, we evaluated if any side effects were exerted also by EDIA, used as single agents or in combination with anthracyclines. Furthermore, we compared the in vitro and in vivo cardiotoxic effects of EDIA with those of the other available anti-ErbB2 drugs: Trastuzumab, 2C4 (Pertuzumab), and Lapatinib. In this article, we show that EDIA, in contrast with Trastuzumab, 2C4, and Lapatinib, have no toxic effects on human fetal cardiomyocytes in vitro, and do not induce additive toxicity when combined with doxorubicin. Furthermore, EDIA do not impair cardiac function in vivo in mice, as evaluated by Color Doppler echocardiography, whereas Trastuzumab significantly reduces radial strain (RS) at day 2 and fractional shortening (FS) at day 7 of treatment in a fashion similar to doxorubicin. Also 2C4 and Lapatinib significantly reduce RS after only 2 days of treatment, even though they showed cardiotoxic effects less pronounced than those of Trastuzumab. These results strongly indicate that RS could become a reliable marker to detect early cardiac dysfunction and that EDIA could fulfill the therapeutic need of patients ineligible to Trastuzumab treatment because of cardiac dysfunction.

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Section: Discussionmentioning

confidence: 99%

Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors

Fedele

Riccio

Coppola

et al. 2011

Breast Cancer Res Treat

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“…Cependant, l'analyse groupée des récentes études, en termes de tolérance, semble montrer un moindre risque de cardiotoxicité, y compris chez les patientes précédemment traitées par anthracyclines [19]. En revanche, une attention particulière doit être portée à la toxicité digestive (diarrhée) et cutanée de l'association lapatinib plus capécitabine, dans cette population fragile des sujets âgés.…”

Section: Dossierunclassified

The place of targeted therapies in the treatment of breast cancer in elderly women

Spano

Théry

2011

Oncologie

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The increased incidence of breast cancer in elderly women leads us to consider the use of targeted therapies specifically in this population. Indeed, these treatments have contributed to a significant improvement in progression free survival and overall survival of patients with breast cancer. In the absence of studies confined to the elderly population, oncogeriatricians have a duty not only to collect objective data on efficacy and safety of targeted therapy from primary studies, but also to employ the oncogeriatric assessment process to look for the criteria of frailty specific to the elderly patient. As previously for chemotherapy, onco-geriatricians must deal with the lack of appropriate data and be content with sub-group information, from which the reliability of the evidence is uncertain. In this review, we examine data available in the literature on the use of targeted therapies in the management of breast cancer in elderly women, so as to guide the clinician in his choice of therapy and his management of toxicity in this growing population. To cite this journal: Oncologie 13 (2011).

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“…Cardiac functions have been analyzed in more than 3,000 patients treated with lapatinib in 18 Phase I-III clinical trials [17]. LVEF was decreased in 1.6% of patients (1.4% was asymptomatic, 0.2% symptomatic).…”

Section: Side Effects Of Trastuzumab and Lapatinibmentioning

confidence: 99%

Treatment strategy for HER2-positive breast cancer

Mukai

2010

Int J Clin Oncol

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HER2-positive tumors account for approximately 18-20% of all breast cancers. These tumors tend to be more aggressive than HER2-negative tumors and are associated with a poorer prognosis. HER2 overexpression, as determined by either 3+ immunohistochemical staining for HER2 protein or HER2 gene amplification by fluorescence in situ hybridization, should be used to select patients for anti-HER2 therapy. Trastuzumab-containing regimens as first-line therapy should be recommended to women with HER2-positive metastatic breast cancer. The continuation of trastuzumab plus capecitabine provided a significant clinical benefit compared with capecitabine alone in women who experienced progression during trastuzumab treatment. An adjuvant trastuzumab-containing regimen should be also recommended to all intermediate- or high-risk women with HER2-positive early breast cancer. Cardiac function should be serially monitored during this treatment. Many anti-HER2 drugs against breast cancer are being developed. The basic mechanisms of their action and resistance emergence are being clarified step by step. Over the mid- or long term, clinical trials comparing these drugs will be conducted until drugs that are clinically effective and easy to use in the true sense survive. Biomarkers are being aggressively searched for concerning individual drugs under development. A position of the "proper drug for the proper patient" will be more firmly established.

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Cardiac Safety of Lapatinib: Pooled Analysis of 3689 Patients Enrolled in Clinical Trials

Cited by 282 publications

References 20 publications

Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors

Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors

The place of targeted therapies in the treatment of breast cancer in elderly women

Treatment strategy for HER2-positive breast cancer

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