DURHAM, NC – A recent FDA-approved combination of therapies used to target HER2-positive breast cancer does not lead to increased cardiac problems for patients, but doctors should regularly perform cardiac monitoring on their cancer patients until additional long-term cardiac safety data become available, according to the first phase III study of the combined treatments. The study, published in The Oncologist, was led by Dr. Sandra M. Swain, MD, Medical Director of the Washington Cancer Institute at Medstar Washington Hospital Center, in collaboration with an international team of researchers.
HER2 – a type of protein found in more aggressive types of breast cancer – is commonly treated with trastuzumab, which has been associated with certain types of cardiac dysfunction. A newer therapy, pertuzumab had undergone limited testing for cardiac safety both alone and in combination with trastuzumab, but Dr. Swain’s study, called CLEOPATRA, was the first phase III trial to study the use of trastuzumab, pertuzumab and docetaxel in patients with HER2-positive metastatic breast cancer receiving first-line treatment.
A randomized, double-blind trial in which some patients received a placebo instead of pertuzumab, CLEOPATRA produced efficacy results that led the FDA last year to approve using a combination of trastuzumab, pertuzumab and docetaxel to treat HER2-positive metastatic breast cancer. As part of this study, Dr. Swain and colleagues examined more than 800 patients’ cardiac incidences during treatment and up to three years after treatment, finding that the drug combination did not contribute to increased heart problems.
“The overall incidence of cardiac adverse effects was low; importantly, the combination of pertuzumab with trastuzumab and docetaxel did not increase the incidence of cardiac adverse effects compared with the placebo arm,” Dr. Swain said.
Researchers used echocardiography or multiple-gated acquisition scanning (MUGA) to assess patients’ left ventricular ejection fraction (LVEF) before treatment, at 9-week intervals during treatment, and once or twice a year after treatment. Adverse cardiac events were reported and graded. Left ventricular systolic dysfunction (LVSD) was the most frequently reported cardiac event, and the majority of cardiac adverse effects were reversible and clinically manageable.
As additional, longer-term data regarding the cardiac impact of this combination therapy continue to be collected, Dr. Swain and colleagues recommend that routine cardiac monitoring of cancer patients be conducted in clinical practice, such as measuring LVEF before the treatment regimen and in 3-month intervals during treatment. Noting the predictive limitations of echocardiograms and MUGA, they also recommended that the optimal schedule for longer-term monitoring should be established in a clinical environment.
“Dr. Swain's analysis of a major breast cancer clinical trial provides fundamental guidance for the treatment of breast cancer patients in which efficacy is maximized and heart toxicities are greatly reduced or eliminated. As such, this is a vital advance by a global leader in oncology,” said Dr, Martin J. Murphy, Jr., Executive Editor of The Oncologist.
The full article, titled “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,” can be accessed at www.TheOncologist.com.
About The Oncologist: Established by oncologists to help physicians better manage their practices in an ever-changing environment, The Oncologist® is the official journal of the Society for Translational Oncology (STO). Now in its 18th year, this internationally peer-reviewed journal focuses on clear and concise interpretation addressing the multimodality diagnosis, treatment, and quality of life of the cancer patient. Each issue is meant to impact the practice of oncology and to facilitate significant communication in the introduction of new medical treatments and technologies. For more information, visit www.TheOncologist.com.
About AlphaMed Press: Established in 1983, AlphaMed Press, with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (www.StemCells.com), which celebrated its 31st year in 2013, is the world's first journal devoted to this fast paced field of research. The Oncologist® (www.TheOncologist.com), entering its 18th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (www.StemCellsTM.com), in its second year, is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.