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

Autor:	Flaherty KT; Massachusetts General Hospital, Boston, MA, USA., Gray R; Dana Farber Cancer Institute ECOG-ACRIN Biostatistics Center, Boston, MA, USA., Chen A; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Li S; Dana Farber Cancer Institute ECOG-ACRIN Biostatistics Center, Boston, MA, USA., Patton D; Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Bethesda, MD, USA., Hamilton SR; University of Texas MD Anderson Cancer Center, Houston, TX, USA., Williams PM; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Mitchell EP; Thomas Jefferson University Hospital, Philadelphia, PA, USA., Iafrate AJ; Massachusetts General Hospital, Harvard University, Boston, MA, USA., Sklar J; Yale University, New Haven, CT, USA., Harris LN; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., McShane LM; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Rubinstein LV; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Sims DJ; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Routbort M; University of Texas MD Anderson Cancer Center, Houston, TX, USA., Coffey B; Center for Biomedical Informatics and Information Technology, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Fu T; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Zwiebel JA; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Little RF; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Marinucci D; ECOG-ACRIN Cancer Research Group, Philadelphia, PA, USA., Catalano R; ECOG-ACRIN Cancer Research Group, Philadelphia, PA, USA., Magnan R; ECOG-ACRIN Cancer Research Group, Boston, MA, USA., Kibbe W; Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Bethesda, MD, USA., Weil C; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Tricoli JV; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Alexander B; Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA., Kumar S; Mayo Clinic, Rochester, MN, USA., Schwartz GK; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Meric-Bernstam F; University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lih CJ; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., McCaskill-Stevens W; Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, MD, USA., Caimi P; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Takebe N; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Datta V; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Arteaga CL; University of Texas Southwestern Simmons Cancer Center, Dallas, TX, USA., Abrams JS; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA., Comis R; ECOG-ACRIN Cancer Research Group, Philadelphia, PA, USA., O'Dwyer PJ; University of Pennsylvania, Philadelphia, PA, USA., Conley BA; Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2020 Oct 01; Vol. 112 (10), pp. 1021-1029.
DOI:	10.1093/jnci/djz245
Abstrakt:	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. (© The Author(s) 2019. Published by Oxford University Press.)
Databáze:	MEDLINE
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