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/m(2) 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.

• Authors: Sandra M Swain, Michael S Ewer, Javier Cortés, Dino Amadori, David Miles, Adam Knott, Emma Clark, Mark C Benyunes, Graham Ross, José Baselga
• Journal: The oncologist (Oncologist) Vol. 18 Issue 3 Pg. 257-64 ( 2013) ISSN: 1549-490X [Electronic] England
• PMID: 23475636 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Taxoids
• Docetaxel
• Receptor, ErbB-2
• pertuzumab
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Docetaxel
• Double-Blind Method
• Female
• Humans
• Neoplasm Metastasis
• Receptor, ErbB-2 (biosynthesis)
• Stroke Volume (drug effects)
• Taxoids (administration & dosage, adverse effects)
• Trastuzumab
• Ventricular Dysfunction, Left (chemically induced)