Innovations in Precision Medicine Introduced at ASCO 2015
By Lynne Lederman, PhD
During this year’s ASCO Annual Meeting, one of the press briefings addressed the theme of innovation in precision medicine in the twenty-first century. Precision medicine uses individual variability to guide disease prevention and treatment. Advances in proteomics, genomics, metabolomics, and data analyses have increased the likelihood that precision medicine may become a reality.1 Challenges to delivering precision medicine in oncology remain, however, including:
Finding new ways to test therapies based on the biology of the cancer rather than its anatomic site of origin or histology
Learning from every patient, not just the 3% who currently enroll in clinical trials
Analyzing data in new ways
The NCI-MATCH trial, and ASCO’s TAPUR trial and CancerLinQ are proposed as answers to these challenges.
The National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (NCI-MATCH), a phase 2 precision medicine trial (also known as EAY131), was opened by the ECOG-ACRIN Cancer Research Group in mid-August of this year2 (NCT024650603). NCI-MATCH is examining targeted therapies for tumors with specific gene mutations regardless of the cancer type (tissue of origin). Investigators will be drawn from ECOG-ACRIN, Alliance, SWOG, and NRG, and the trial will be conducted throughout the National Clinical Trials Network. The overall outcome goals for NCI MATCH include tumor response and 6-month progression-free survival.
NCI-MATCH is considered the largest precision medicine trial to date. The trial is screening about 3000 adults with cancer that has progressed after treatment with standard therapy; fresh tumor biopsies will be tested for one of 143 genetic mutations (with over 4000 variants) associated with cancer to identify patients eligible for one of 22 treatment options based on those “actionable” mutations. It is assumed that 1000 tested patients will be eligible, of whom about 25% will have a rate type of cancer. The drugs and molecular targets for the first 10 arms of the trial are shown in Table 1.4 Note that some of the agents are pending final regulatory review.
Barbara A. Conley, MD, Associate Director of the Cancer Diagnosis Program (CDP) in the Division of Cancer Treatment and Diagnosis (DCTD), NCI, is the NCI Study Co-Chair. She says they do not know how long it will take to enroll and treat all patients; additional arms will be added by the end of this year (see Figure 1) and if results are promising, even more arms could be added and more patients recruited.
Dr. Conley says that NCI-MATCH is a high priority for the NCI and will be prominent in its budget. “We are moving on the assumption that funding is secure,” she adds. The results will be reported arm by arm, whether positive or not. During the first 3 weeks the trial was open, about 40 patients registered for the first screening step. Dr. Conley says that 20% to 80% of patients could be expected to have “actionable mutations” that could be treated in NCI-MATCH, and the percentage could go up as more arms are added.