Personalized Health Care (PHC) in Cancer - Genomic Biomarkers for Pharmaceutical Development - page 22

CHAPTER
2
Personalized Health Care
(PHC) in Cancer
Nicholas C. Dracopoli 1 , Katie Streicher 2
1 Janssen Research and Development, LLC Radnor, Pennsylvania
2 MedImmune, LLC Gaithersburg, Maryland
2.1 INTRODUCTION
Empirical drug development strategies in oncology are becoming unsustainable. Still,
only ~10% of first in class oncology drugs entering first in human (FIH) testing eventually
obtain regulatory approval [1] . The reasons for this high attrition rate are complex but often
result from poor in vitro and in vivo models which lead to early failure in clinical develop-
ment, or because a poor understanding of the underlying molecular pathology of the dis-
ease leads to the development of the drug in suboptimal indications. Novel approaches
to personalized healthcare are required to reduce the attrition of novel oncology drugs in
development and to improve outcome for cancer patients.
The discovery and application of novel biomarkers is essential for the successful imple-
mentation of personalized healthcare for cancer patients. These biomarkers are used for many
purposes, including validating the mechanism of action (MOA) of a new drug, exploring
pharmacokinetic/pharmacodynamic (PK / PD) interactions, predicting response to therapy,
identifying mechanisms of resistance to therapy, and determining prognosis and disease out-
come. However, converting biomarkers to clinical practice has been difficult. There are 21,403
biomarkers listed in the GVK BIO Online Biomarker (GOBIOM) database (January 31, 2013),
but only 32 of these are listed as valid biomarkers by the Food and Drug Administration
(FDA). All the clinically validated markers are single analyte biomarkers, and no complex
molecular profiles that predict response to therapy have yet been approved by the FDA.
The following sections describe successful examples of personalized healthcare in oncol-
ogy and can be seen as precedents for future development of first in class oncology drugs.
These represent only the first steps using simple biomarkers that measure the status of the
drug target or pathway to predict patient response. Today, a total of 12 drugs have been
approved in oncology with predictive biomarkers. However, these approved drugs only