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Molecular Profiles and Actionable Alterations Identified in the NCI-MATCH Trial


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In a report in the Journal of Clinical Oncology, Keith T. Flaherty, MD, and colleagues describe the current status of and findings from the ongoing NCI-MATCH (National Cancer Institute Molecular Analysis for Therapy Choice) trial. The aim of the trial is to determine the likelihood of identifying molecular alterations across multiple tumor types using next-generation sequencing that can be matched with approved or investigational targeted therapies and to evaluate the activity of these treatments.

Keith T. Flaherty, MD

Keith T. Flaherty, MD

Study Details

In the study, tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites have been analyzed centrally with next-generation sequencing and selected immunohistochemistry in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel single-arm phase II subprotocols.

Key Findings

Molecular profiling was successful in 93.0% (n = 5,540) of specimens.

An actionable alteration was found in 37.6% of specimens. After accounting for molecular, prior treatment, and specific cancer exclusions, the match rate was 26.4%. Lack of subprotocol availability (subprotocol had reached accrual or limit on certain histologic types was reached) resulted in a treatment assignment rate of 17.8% (n = 985 of 5,540).

Among assigned patients, 70% received treatment on a subprotocol. The accrual goal of at least 31 eligible patients had been reached in 11 of 30 subprotocols at the time of reporting.  

Assignment rates for patients with non–small cell lung, colorectal, breast, and prostate cancers were 17.4%, 13.7%, 17.8%, and 23.0%, respectively. Assignment rates were > 25% for individuals with CNS cancer (37.2%), urothelial cancer (36.0%), pancreaticobiliary cholangiocarcinoma (25.9%), cervical cancer (28.4%), gastroesophageal cancer (27.8%), melanoma (26.3%), uterine cancer (26.2%), and anal cancer (25.5%). Low assignment rates were observed for patients with pancreatic cancer (5.8%), small cell lung cancer (5.1%), and lymphoma (5.0%).

Multiple actionable or resistance-conferring tumor mutations were observed in 11.9% and 71.3% of specimens, respectively.

“We demonstrated feasibility of screening large numbers of patients at numerous accruing sites in a complex trial to test investigational therapies for moderately frequent molecular targets. Co-occurring resistance mutations were common and endorse investigation of combination targeted therapy regimens.”
— Keith T. Flaherty, MD, and colleagues

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Molecular alterations in seven tumors profiled in both the NCI-MATCH trial and The Cancer Genome Atlas (TCGA) of primary tumors were compared, with the hypothesis that the genetic complexity of NCI-MATCH samples would be greater given its inclusion of heavily pretreated patients. Co-occurring mutations were found in 52.8% of NCI-MATCH tumors vs 44.1% for TCGA tumors. Known resistance mutations to targeted therapies were numerically more common in NCI-MATCH than TCGA tumors, but no marked differences were observed.

The investigators concluded, “We demonstrated feasibility of screening large numbers of patients at numerous accruing sites in a complex trial to test investigational therapies for moderately frequent molecular targets. Co-occurring resistance mutations were common and endorse investigation of combination targeted therapy regimens.”

Dr. Flaherty, of Massachusetts General Hospital Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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