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The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design.

Publication ,  Journal Article
Flaherty, KT; Gray, R; Chen, A; Li, S; Patton, D; Hamilton, SR; Williams, PM; Mitchell, EP; Iafrate, AJ; Sklar, J; Harris, LN; McShane, LM ...
Published in: J Natl Cancer Inst
October 1, 2020

BACKGROUND: The proportion of tumors of various histologies that may respond to drugs targeted to molecular alterations is unknown. NCI-MATCH, a collaboration between ECOG-ACRIN Cancer Research Group and the National Cancer Institute, was initiated to find efficacy signals by matching patients with refractory malignancies to treatment targeted to potential tumor molecular drivers regardless of cancer histology. METHODS: Trial development required assumptions about molecular target prevalence, accrual rates, treatment eligibility, and enrollment rates as well as consideration of logistical requirements. Central tumor profiling was performed with an investigational next-generation DNA-targeted sequencing assay of alterations in 143 genes, and protein expression of protein expression of phosphatase and tensin homolog, mutL homolog 1, mutS homolog 2, and RB transcriptional corepressor 1. Treatments were allocated with a validated computational platform (MATCHBOX). A preplanned interim analysis evaluated assumptions and feasibility in this novel trial. RESULTS: At interim analysis, accrual was robust, tumor biopsies were safe (<1% severe events), and profiling success was 87.3%. Actionable molecular alteration frequency met expectations, but assignment and enrollment lagged due to histology exclusions and mismatch of resources to demand. To address this lag, we revised estimates of mutation frequencies, increased screening sample size, added treatments, and improved assay throughput and efficiency (93.9% completion and 14-day turnaround). CONCLUSIONS: The experiences in the design and implementation of the NCI-MATCH trial suggest that profiling from fresh tumor biopsies and assigning treatment can be performed efficiently in a large national network trial. The success of such trials necessitates a broad screening approach and many treatment options easily accessible to patients.

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Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

October 1, 2020

Volume

112

Issue

10

Start / End Page

1021 / 1029

Location

United States

Related Subject Headings

  • Young Adult
  • Precision Medicine
  • Oncology & Carcinogenesis
  • Neoplasms
  • Molecular Targeted Therapy
  • Middle Aged
  • Male
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Female
 

Citation

APA
Chicago
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Flaherty, K. T., Gray, R., Chen, A., Li, S., Patton, D., Hamilton, S. R., … NCI-MATCH Team, . (2020). The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design. J Natl Cancer Inst, 112(10), 1021–1029. https://doi.org/10.1093/jnci/djz245
Flaherty, Keith T., Robert Gray, Alice Chen, Shuli Li, David Patton, Stanley R. Hamilton, Paul M. Williams, et al. “The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design.J Natl Cancer Inst 112, no. 10 (October 1, 2020): 1021–29. https://doi.org/10.1093/jnci/djz245.
Flaherty KT, Gray R, Chen A, Li S, Patton D, Hamilton SR, et al. The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design. J Natl Cancer Inst. 2020 Oct 1;112(10):1021–9.
Flaherty, Keith T., et al. “The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design.J Natl Cancer Inst, vol. 112, no. 10, Oct. 2020, pp. 1021–29. Pubmed, doi:10.1093/jnci/djz245.
Flaherty KT, Gray R, Chen A, Li S, Patton D, Hamilton SR, Williams PM, Mitchell EP, Iafrate AJ, Sklar J, Harris LN, McShane LM, Rubinstein LV, Sims DJ, Routbort M, Coffey B, Fu T, Zwiebel JA, Little RF, Marinucci D, Catalano R, Magnan R, Kibbe W, Weil C, Tricoli JV, Alexander B, Kumar S, Schwartz GK, Meric-Bernstam F, Lih C-J, McCaskill-Stevens W, Caimi P, Takebe N, Datta V, Arteaga CL, Abrams JS, Comis R, O’Dwyer PJ, Conley BA, NCI-MATCH Team. The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design. J Natl Cancer Inst. 2020 Oct 1;112(10):1021–1029.
Journal cover image

Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

October 1, 2020

Volume

112

Issue

10

Start / End Page

1021 / 1029

Location

United States

Related Subject Headings

  • Young Adult
  • Precision Medicine
  • Oncology & Carcinogenesis
  • Neoplasms
  • Molecular Targeted Therapy
  • Middle Aged
  • Male
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Female