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

Conclusions

Advances in biotechnology and bioinformatics over the past decade have allowed for molecular characterization of patient tumors, opening opportunities for the development of tailored therapeutics based on characterization of a patient's tumor. The Precision Medicine Initiative is a priority for the NCI, and was recently noted during President Obama's 2014 State of the Union address.[12] Currently the NCI is sponsoring several trials strategized to test the benefit of targeted therapy. NCI MATCH, MPACT and Exceptional Responder initiative are among these trials. Others including lung MAP and ALCHEMIST will be discussed by others in this journal. The results of the Exceptional Responders initiative in particular will be central to the identification of molecular features of tumors that would predict for response to a particular drug or class of drugs. For many currently standard chemotherapy drugs or regimens, the exact mechanism of action may not be known, and thus Exceptional Responders to such regimens may provide critical new data. The information obtained from this trial will be made available to investigators in a database that can be shared, built upon, and further mined. The NCI MATCH trial will evaluate these targets and whether they behave similarly across histologic subtypes. The provocative MPACT trial further seeks to address the larger question of the importance of targeting "actionable mutations" with targeted agents, and whether this will translate into meaningful clinical benefit above that achieved by current treatments.

The premise of both the NCI MATCH and MPACT trials relies heavily on the precision and accuracy of molecular tumor characterization techniques to find the target. Predefined rules allow for the elimination of bias from the selection process and allow for rapid decision-making once molecular targets are identified. Both trials also require a reliable informatics system to process the results of the assay and output of treatment selection. From a patient aspect, this process must additionally be sufficiently rapid to provide meaningful treatment options for patients willing to undergo biopsy and remain untreated while awaiting results. Additionally, with the continuing explosion of genomic data being generated, this cannot be a static process. The structure of these trials allows for flexibility with these changing data, allowing for addition of new variants and targets, and the removal of ineffective ones. By building in biopsies at the point of progression, these trials will also allow for a broader understanding of resistance mechanisms invoked with exposure to subsequent therapies and the intricate interplay between these molecular pathways.

Additional factors which need to be considered in implementation of these transformative trials involve the management of reporting of genomic data. Reporting of incidental findings to patients requires forethought, especially in situations of mutations of unknown significance. Results from these trials will provide a strong structure to build new and better treatment options for oncology patients in the twenty-first century. As a consequence, oncologists will increasingly be called upon to deal with assisting patients to understand the vast amount of genetic data generated from these studies and how best to use the information to assist in management of their cancer. With the evolution of vast amounts of information and the identification of smaller and smaller subpopulations of patients who would benefit from any one particular therapy, the question of how these particular treatments will garner regulatory approval remains to be seen.

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