Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: A randomized, double-blind, placebo-controlled phase III study Journal Article


Authors: Swain, S. M.; Ewer, M. S.; Cortes, J.; Amadori, D.; Miles, D.; Knott, A.; Clark, E.; Benyunes, M. C.; Ross, G.; Baselga, J.
Article Title: Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: A randomized, double-blind, placebo-controlled phase III study
Abstract: Introduction. We report cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel observed in the phase III study CLEOPATRA in patients with HER2-positive first-line metastatic breast cancer (MBC). Patients and Methods. Left ventricular ejection fraction (LVEF) ≥50% and ECOG performance status of 0 or 1 were required for study entry. During the study, LVEF assessments took place every 9 weeks. Pertuzumab/placebo was given at 840 mg, then 420 mg q3w; trastuzumab was administered at 8 mg/kg, then 6 mg/kg q3w, and docetaxel was initiated at 75 mg/m2 q3w. Results. The incidence of cardiac adverse events (all grades) was 16.4% in the placebo arm and 14.5% in the pertuzumab arm, with left ventricular systolic dysfunction (LVSD, all grades) being the most frequently reported event (8.3% versus 4.4% in the placebo and pertuzumab arm). Declines in LVEF ≥by 10% points from baseline and to <50% were reported in 6.6% and 3.8% of patients in the placebo and pertuzumab arm, respectively. Seventy-two percent (placebo arm) and 86.7% (pertuzumab arm) of those patients recovered to a value ≥50%. The incidence of symptomatic LVSD was low, occurring in 1.8% (n 7) versus 1.0% (n 4) of patients in the placebo and pertuzumab arm. In 8/11 patients, the symptomatic LVSD had resolved at data cutoff. Conclusion. The combination of pertuzumab plus trastuzumab plus docetaxel did not increase the incidence of cardiac adverse events, including LVSD, compared with the control arm in HER2-positive MBC. The majority of cardiac adverse events were reversible. © AlphaMed Press 2013.
Keywords: adult; controlled study; aged; major clinical study; disease course; drug tolerability; doxorubicin; placebo; drug safety; drug withdrawal; hypertension; multiple cycle treatment; heart disease; antineoplastic combined chemotherapy protocols; incidence; epidermal growth factor receptor 2; smoking; bradycardia; breast neoplasms; risk factor; docetaxel; heart palpitation; heart failure; heart infarction; diabetes mellitus; neoplasm metastasis; receptor, erbb-2; taxoids; heart arrhythmia; trastuzumab; breast metastasis; double-blind method; heart left ventricle ejection fraction; metastatic breast cancer; pericardial effusion; heart atrium fibrillation; congestive heart failure; heart ventricle arrhythmia; heart ventricle fibrillation; stroke volume; supraventricular tachycardia; tachycardia; heart muscle ischemia; her2; pericarditis; pertuzumab; sinus tachycardia; sinus bradycardia; randomized controlled trial (topic); cardiomegaly; phase 3 clinical trial (topic); angina pectoris; ventricular dysfunction, left; antibodies, monoclonal, humanized; cardiac safety; left ventricular systolic dysfunction; lvsd; diastolic dysfunction; heart atrium thrombosis; heart right bundle branch block; heart ventricle extrasystole; mitral valve regurgitation; supraventricular premature beat
Journal Title: The Oncologist
Volume: 18
Issue: 3
ISSN: 1083-7159
Publisher: AlphaMed Press  
Date Published: 2013-01-01
Start Page: 257
End Page: 264
Language: English
PROVIDER: scopus
PMCID: PMC3607520
PUBMED: 23475636
DOI: 10.1634/theoncologist.2012-0448
DOI/URL:
Notes: --- - "Export Date: 1 May 2013" - "CODEN: OCOLF" - ":doi 10.1634/theoncologist.2012-0448" - ": Chemicals/CASdocetaxel, 114977-28-5; doxorubicin, 23214-92-8, 25316-40-9; epidermal growth factor receptor 2, 137632-09-8; trastuzumab, 180288-69-1" - "Source: Scopus"
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  1. Jose T Baselga
    404 Baselga