Development of Targeted Agents and Companion Diagnostics
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Development of Targeted Agents and Companion Diagnostics Be´atrice Gerard, MD1, Marie-Christine Be´tard, PhD2, Bradley Smith, PhD3, and Madlyn Denyer, PhD4
Abstract This article summarizes a presentation made at the joint BIA/MHRA conference, ‘‘Challenges of Development of Targeted Agents and Companion Diagnostics,’’ in London in March 2011. It focuses on the challenges the pharmaceutical industry is facing with the development of targeted agents in the field of oncology, in parallel with the challenges associated with the identification and development of the necessary diagnostic tools to support patient selection for personalized therapy. This article will encompass clinical, technical, and regulatory aspects. Keywords personalized medicine, companion diagnostic test, predictive biomarker, targeted therapy
Introduction Background In the modern oncology field, personalized medicine is becoming more recognized and accepted as the solution for providing better and quicker therapy outcomes to patients with limited life expectancy. Over the last decade, accumulated experience and the body of evidence on the outcome with targeted agents (TAs) in selected and unselected patients have grown. This experience demonstrates that the treatment of patient populations based solely on cancer type and histological parameters is no longer viable due to limited efficacy, lower than expected benefit/risk ratio, and hence excessive cost. New approaches based on subdividing patient populations into different molecular diseases according to relevant oncogenic drivers and pathways should now become the practice. This is all the more critical when the sensitizing genetic alteration is present only in a small subset of patients. In this case, there is a very limited possibility that a response signal can be detected in the course of a standard development strategy in an unselected patient population. Therefore, it is hoped that in order to provide quick and efficient information to the clinician as to the choice of the most relevant TA, the molecular characterization of the patient and the patient’s tumor using high-throughput technologies should assess as many molecular alterations as possible with the intent of defining a profile of potentially effective agents/ combinations of agents. Eventually, the approach to drug development of using patient-individualized molecular/genetic
tumor profiles to define which patients are enrolled into a prospective trial will become standard practice. A more focused approach of performing a series of gene expression–guided pilot studies, each with a single patient, is under investigation.1 To bring these approaches into wider practice, the current limitations of access to tumor samples, in particular when no surgically removed tissue is available, and the cost of the procedures will have to be overcome. Easier access to tumor cells is under investigation using circulating tumor cells or free DNA. In this article, we will restrict our focus to ‘‘personalized medicine’’ as defined by the Council of Adv
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