Cardiac safety of lapatinib: Pooled analysis of 3689 patients enrolled in clinical trials

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

Research output: Contribution to journalArticle

283 Citations (Scopus)

Abstract

OBJECTIVE: To analyze the cardiac safety of lapatinib, an oral, reversible, tyrosine kinase EGFR (ERBB1) and HER2 inhibitor, using prospective data collected in 44 clinical studies. PATIENTS AND METHODS: Lapatinib (as monotherapy or in combination) was administered to 3689 patients in studies conducted between January 5, 2001, and September 30, 2006. Left ventricular ejection fraction (LVEF) was prospectively evaluated via multiple-gated acquisition scan or echocardiography at screening, every 8 weeks during therapy, and at withdrawal. We analyzed cardiac events defined as symptomatic (grade 3 or 4 left ventricular systolic dysfunction according to the National Cancer Institute Common Terminology Criteria for Adverse Events) or asymptomatic (LVEF decreases ?20% relative to baseline and below the institution's lower limit of normal; no symptoms). RESULTS: A study-defined cardiac event was reported in 60 patients (1.6%) previously treated with anthracyclines (n=12), trastuzumab (n=14), or neither (n=34). These prior treatments were associated with a 2.2%, 1.7%, and 1.5% incidence of cardiac events, respectively. In most patients (53 patients, 83%), events were not preceded by symptoms. Mean times to onset and duration of LVEF decrease were 13.0 and 7.3 weeks, respectively. The decrease in LVEF was rarely severe; the mean nadir was 43%. In 40 patients for whom outcome was determined, 35 (88%) had a partial or full recovery regardless of continuation or discontinuation of lapatinib. No cardiac deaths occurred among patients treated with lapatinib. CONCLUSION: Our review of data from 44 clinical studies revealed low levels of cardiotoxicity for lapatinib. Cardiac events were usually asymptomatic, caused reversible decreases in LVEF, and occurred at similar rates in patients who were and were not pretreated with anthracyclines or trastuzumab.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalMayo Clinic Proceedings
Volume83
Issue number6
DOIs
StatePublished - 2008

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Clinical Trials
Stroke Volume
Safety
Anthracyclines
National Cancer Institute (U.S.)
Left Ventricular Dysfunction
lapatinib
Terminology
Protein-Tyrosine Kinases
Echocardiography
Incidence
Therapeutics
Clinical Studies
Trastuzumab

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Perez, E. A., Koehler, M., Byrne, J., Preston, A. J., Rappold, E., & Ewer, M. S. (2008). Cardiac safety of lapatinib: Pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clinic Proceedings, 83(6), 679-686. https://doi.org/10.4065/83.6.679

Cardiac safety of lapatinib : Pooled analysis of 3689 patients enrolled in clinical trials. / Perez, Edith A.; Koehler, Maria; Byrne, Julie; Preston, Alaknanda J.; Rappold, Erica; Ewer, Michael S.

In: Mayo Clinic Proceedings, Vol. 83, No. 6, 2008, p. 679-686.

Research output: Contribution to journalArticle

Perez, EA, Koehler, M, Byrne, J, Preston, AJ, Rappold, E & Ewer, MS 2008, 'Cardiac safety of lapatinib: Pooled analysis of 3689 patients enrolled in clinical trials', Mayo Clinic Proceedings, vol. 83, no. 6, pp. 679-686. https://doi.org/10.4065/83.6.679
Perez, Edith A. ; Koehler, Maria ; Byrne, Julie ; Preston, Alaknanda J. ; Rappold, Erica ; Ewer, Michael S. / Cardiac safety of lapatinib : Pooled analysis of 3689 patients enrolled in clinical trials. In: Mayo Clinic Proceedings. 2008 ; Vol. 83, No. 6. pp. 679-686.
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abstract = "OBJECTIVE: To analyze the cardiac safety of lapatinib, an oral, reversible, tyrosine kinase EGFR (ERBB1) and HER2 inhibitor, using prospective data collected in 44 clinical studies. PATIENTS AND METHODS: Lapatinib (as monotherapy or in combination) was administered to 3689 patients in studies conducted between January 5, 2001, and September 30, 2006. Left ventricular ejection fraction (LVEF) was prospectively evaluated via multiple-gated acquisition scan or echocardiography at screening, every 8 weeks during therapy, and at withdrawal. We analyzed cardiac events defined as symptomatic (grade 3 or 4 left ventricular systolic dysfunction according to the National Cancer Institute Common Terminology Criteria for Adverse Events) or asymptomatic (LVEF decreases ?20{\%} relative to baseline and below the institution's lower limit of normal; no symptoms). RESULTS: A study-defined cardiac event was reported in 60 patients (1.6{\%}) previously treated with anthracyclines (n=12), trastuzumab (n=14), or neither (n=34). These prior treatments were associated with a 2.2{\%}, 1.7{\%}, and 1.5{\%} incidence of cardiac events, respectively. In most patients (53 patients, 83{\%}), events were not preceded by symptoms. Mean times to onset and duration of LVEF decrease were 13.0 and 7.3 weeks, respectively. The decrease in LVEF was rarely severe; the mean nadir was 43{\%}. In 40 patients for whom outcome was determined, 35 (88{\%}) had a partial or full recovery regardless of continuation or discontinuation of lapatinib. No cardiac deaths occurred among patients treated with lapatinib. CONCLUSION: Our review of data from 44 clinical studies revealed low levels of cardiotoxicity for lapatinib. Cardiac events were usually asymptomatic, caused reversible decreases in LVEF, and occurred at similar rates in patients who were and were not pretreated with anthracyclines or trastuzumab.",
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