Applied Clinical Trials eBook - June 2014 - (Page 6)
ONCOLOGY
New Road of Cardio-Oncology
in Clinical Development
David S. Herron
The prevalence of cardiovascular toxicity associated
with oncology drugs triggers a new discipline.
T
he prevalence of cardiovascular toxicity associated with oncology drugs has resulted
in increased public, regulatory, and industry
awareness for cardiovascular (CV) safety within
oncology drug development. It has also triggered a new clinical discipline called cardio-oncology that aims to bridge the gap between cardiology
and oncology and promote safer drugs and better
outcomes for cancer patients.
For drug sponsors, this means rethinking design of
routine clinical trials and implementing effective CV
safety strategies to evaluate potential drug induced
cardiotoxicity. The benefits of an effective cardiooncology strategy are long lasting, both from a clinical perspective (improved patient outcomes) and an
economic one (getting a successful drug to market).
Advances in technology and our understanding
of cardiotoxicity mechanisms have resulted in improved CV safety monitoring strategies, which include endpoints for cardiac performance (i.e., left
ventricular function; LVF), cardiac electrophysiology
(i.e., electrocardiograms; ECGs), and hemodynamics
(i.e., blood pressure; BP). Taken together, sponsors
are empowered to take a multi-pronged, comprehensive approach to CV safety in their clinical trials.
LVF, the most clinically relevant endpoint for cardiotoxicity associated with chemotherapeutic agents,
is primarily assessed by imaging modalities such as
echocardiography, cardiac MRI, and, to a lesser extent, MUGA and CT. Recent advances in cardiac modalities, including Tissue Doppler imaging and myocardial deformation imaging, are paving the way for
increasingly sensitive detection of cardiac dysfunction.
Current FDA data indicate that oncology drugs
are most frequently associated with QT prolongation
(indicative of potential pro-arrhythmia) compared
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to other therapeutic areas. This fact, coupled with a
formal regulatory guidance issued by the International
Conference on Harmonization (ICH-E14) that requires
sponsors to assess ECG QT intervals using a formal
thorough QT study, has prompted a fresh review of
oncology drug-induced QT prolongation and proarrhythmia. The assessment of cancer drugs using
this method presents unique challenges for sponsors
due to high drug toxicity, narrow therapeutic windows,
disease comorbidities, and placebo use. Advances
in ECG technology provide sponsors and sites with
increased capabilities for digital ECG acquisition, electronic data transfer, algorithm-guided analysis, and
data reproducibility in support of regulatory approvals.
Targeted therapies which attack tumor vasculature
can have systemic adverse effects on blood pressure,
with the potential for causing acute or chronic hypertension. Advancements in blood pressure technologies enable automated and ambulatory BP endpoints
to be integrated into a study protocol, providing
sponsors with accurate and robust datasets for a better understanding of drug safety profiles. Additionally,
the increased portability and improved functionality
of BP devices enable data capture and electronic
submission directly from a patient's home, increasing
patient participation and protocol compliance.
With a growing number of CV safety approaches,
sponsors must select and implement appropriate
endpoints to determine and mitigate the risks associated with new cancer drugs. As the CV safety paradigm shifts to a more integrated approach, sponsors are relying on complimentary methodologies
to gain a complete picture of a drug's safety profile.
David S. Herron Executive VP and President, Medical
Imaging and Cardiac Core Lab Division, BioClinica, Inc.
June 2014
http://www.appliedclinicaltrialsonline.com
Table of Contents for the Digital Edition of Applied Clinical Trials eBook - June 2014
Applied Clinical Trials eBook - June 2014
Contents
Analyzing 2013 Oncology Trends to Predict 2014 Directions
New Road of Cardio-Oncology in Clinical Development
Partnering Early for Successful Oncology Drug Development
Translational Medicine and Biomarkers
Immunotherapy Clinical Trials in Melanoma
Patient-First Approach to Improve Oncology Clinical Trials
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