An Overview of the NCI Precision Medicine Trials—NCI MATCH and MPACT

Khanh Do; Geraldine O'Sullivan Coyne; Alice P. Chen

Disclosures

Chin Clin Oncol. 2015;4(3):2304-3865. 

In This Article

Background

The concept of oncogene addiction was first proposed by Weinstein,[1] and has led to a whole new approach to cancer treatment. The discovery of imatinib, the Bcr-Abl tyrosine kinase inhibitor, in the treatment of chronic myelogenous leukemia, revolutionized treatment paradigms with regard to targeted therapies, as this was the first targeted agent to illustrate the concept that treating the principal driving oncogene can have a powerful impact on response.[2] More recent efforts to catalog driver mutations across the entire cancer population have led to the development of a plethora of targeted agents. Subsequent generations of molecularly targeted agents have effectively subcategorized tumors into smaller molecular subsets, such as EGFR and ALK inhibitors in non-small cell lung cancer and BRAF inhibitors in melanoma, in an effort to duplicate this success. As a further example, trastuzumab has received approval for gastro-esophageal and gastric cancers in addition to HER2 overexpressing breast cancers.[3,4] These efforts have led to the realization that the targeting of these mutations has the potential to transcend tumor histologies, effectively categorizing tumors based on the molecular signature.

Recent advances in biotechnology and bioinformatics over the past decade have led to a greater appreciation for the heterogeneity of tumors and the complex signaling pathways involved in the resistance to treatment. This complexity requires a network-based streamlined approach to the interpretation of data generated from a profile of the tumor. The current challenge of clinical trial design is focused upon the identification of molecular alterations in tumors and the selection for those patients who would be most likely to benefit from a particular targeted therapy. The Division of Cancer Diagnosis and Treatment of the United States National Cancer Institute (NCI) has accepted this challenge and is presently engaged in several trials dedicated to precision-based medicine (http://dctd.cancer.gov/MajorInitiatives/NCI-sponsored_trials_in_precision_medicine.htm). The NCI Molecular Analysis for Therapy Choice (MATCH), Molecular Profiling-based Assignment of Cancer Therapy (MPACT), and Exceptional Responders study are among these trials.

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