The Molecular Analysis for Therapy Choice (NCI-MATCH) Trial: Lessons for Genomic Trial Design.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ administration & dosage
Biopsy
Clinical Trial Protocols as Topic
Clinical Trials, Phase II as Topic
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Molecular Targeted Therapy
Neoplasms
/ drug therapy
Precision Medicine
Young Adult
Journal
Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
22
07
2019
revised:
02
12
2019
accepted:
26
12
2019
pubmed:
11
1
2020
medline:
20
4
2021
entrez:
11
1
2020
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 31922567
pii: 5699915
doi: 10.1093/jnci/djz245
pmc: PMC7566320
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1021-1029Subventions
Organisme : NCI NIH HHS
ID : U24 CA196172
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233180
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180820
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180794
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180853
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press.
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