THE NATIONAL CANCER INSTITUTE (NCI) Molecular Analysis for Therapy Choice (MATCH) clinical trial has achieved the goal of screening nearly 6,000 patients in just under 2 years, according to data presented at the 2017 American Association for Cancer Research–NCI–European Organisation for Research and Treatment of Cancer International Conference on Molecular Targets and Cancer Therapeutics.1 The genomic study was led by Alice P. Chen, MD, Head of the Early Clinical Trials Development Program in the Division of Cancer Treatment and Diagnosis at the NCI. NCI-MATCH is the first national signal-finding trial to incorporate centralized national geodetic survey testing to direct patients to molecularly targeted parallel phase II treatment arms.
Alice P. Chen, MD
Study Details
ELIGIBLE PATIENTS for NCI-MATCH have advanced or refractory solid tumors, lymphoma, or myeloma with a molecular abnormality believed to predict response. The most common types of cancer accounted for 38.2% of the cancers screened [colorectum (15.4%), breast (12.8%), lung (7.4%), prostate (2.6%)], with 61.8% having rarer cancer types. Of the tumors screened, 18% were found to have a genetic mutation that matched the patient to 1 of the 30 treatment arms.
“NCI-MATCH is a precision medicine clinical trial designed to explore signals of treating patients based on their molecular aberration regardless of the histology of their tumor,” said Dr. Chen. “If 25% or more of the patients with a given mutation that matches them to a specific treatment arm respond to the treatment, it would mean the particular treatment-mutation combination is worthy of further study in a larger phase II clinical trial.”
As of July 2017, 5,963 tumor samples from patients with a wide range of cancer types at more than 1,000 clinical sites across the United States had been screened using next-generation sequencing at 1 of 4 central gene-sequencing laboratories. The sequencing assay successfully yielded a result 93% of the time, which is well above the industry average of about 80%, according to Dr. Chen. Such success reflects a promising future of genomics and the NCI-MATCH study. “The activity of each drug will be analyzed when 31 to 70 patients have been treated to determine whether matching drugs to molecular targets results in improved patient outcome and what tumor types are more likely to respond,” noted Dr. Chen.
Study Limitations
PATIENT ACCRUAL to each arm has been variable. Of all the treatment arms, 8 of the 30 reached the minimum patient accrual goal of 35, and some of them have been expanded to allow for accrual of up to 70 patients. As a result of the low prevalence rate of some of the mutations, some of the treatment arms did not accrue 35 patients within the initial screening cohort of nearly 6,000 patients.
According to Dr. Chen, the main limitations of the study are that the sample size for each treatment arm is relatively small, indicating the number of cases with a particular histology for a given treatment may be limited, and the patients referred to the trial tend to be heavily pretreated, making broad applicability limited as well. However, if there is a signal in a heavily pretreated population, it suggests potentially exciting activity for the agent that can then be followed up on in additional trials that target the responding population.
DISCLOSURE: Dr. Chen reported no conflicts of interest.
REFERENCE
1. Harris L, Chen A, O’Dwyer P, et al: Update on the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH/EAY131) precision medicine trial. 2017 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Abstract B080. Presented October 29, 2017.
