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Updated: Jul 19, 2026

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
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Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer

Keith T Flaherty1, Robert J Gray2, Alice P Chen3

  • 1Massachusetts General Hospital, Boston, MA.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|October 13, 2020
PubMed
Abstract

Insights

The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial successfully screened many patients for targeted cancer therapies. Actionable molecular alterations were common, supporting combination targeted-therapy investigations.

Area of Science:

  • Translational oncology
  • Precision medicine
  • Molecular diagnostics

Background:

  • Therapeutically actionable molecular alterations are present across diverse cancer types.
  • Evaluating targeted therapy efficacy in less common cancer types requires innovative trial designs.

Purpose of the Study:

  • To assess the antitumor activity of targeted therapies in cancers with underexplored molecular alterations.
  • To establish the feasibility of a master screening protocol for a large-scale targeted therapy trial.

Main Methods:

  • Centralized next-generation sequencing (NGS) and immunohistochemistry of 5,954 tumor biopsy specimens from patients with refractory malignancies.
  • Assignment of patients to parallel, single-arm, phase II subprotocols based on identified actionable molecular alterations.
  • Comparison of molecular alterations in NCI-MATCH tumors versus The Cancer Genome Atlas (TCGA) primary tumors for seven cancer types.

Main Results:

  • Molecular profiling was successful in 93.0% of specimens, identifying actionable alterations in 37.6%.
  • 17.8% of patients were assigned to treatment arms, with actionability rates varying significantly by histology.
  • Co-occurring actionable or resistance-conferring mutations were found in 11.9% and 71.3% of specimens, respectively.

Conclusions:

  • Demonstrated the feasibility of large-scale patient screening for targeted therapies in a complex trial setting.
  • The common occurrence of co-occurring resistance mutations supports the investigation of combination targeted-therapy regimens.

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