@article{902cef8389f74c1dac6b249f5ce4226c,
title = "Trametinib activity in patients with solid tumors and lymphomas harboring braf non-V600 mutations or fusions: Results from NCI-MATCH (EAY131)",
abstract = "Purpose: Substantial preclinical evidence and case reports suggest thatMEKinhibition is an active approach in tumors with BRAF mutations outside the V600 locus, and in BRAF fusions. Thus, Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in this population. Patients and Methods: The NCI-MATCH study performed genomic profiling on tumor samples from patients with solid tumors and lymphomas progressing on standard therapies or with no standard treatments. Patients with prespecified fusions and non- V600 mutations in BRAF were assigned to Subprotocol R using the NCI-MATCHBOX algorithm. The primary endpoint was objective response rate (ORR). Results: Among 50 patients assigned, 32 were eligible and received therapy with trametinib. Of these, 1 had a BRAF fusion and 31 had BRAF mutations (13 and 19 with class 2 and 3 mutations, respectively). There were no complete responses; 1 patient (3%) had a confirmed partial response (patient with breast ductal adenocarcinoma with BRAF G469E mutation) and 10 patients had stable disease as best response (clinical benefit rate 34%). Median progression-free survival (PFS) was 1.8 months, and median overall survival was 5.7 months. Exploratory subgroup analyses showed that patients with colorectal adenocarcinoma (n = 8) had particularly poor PFS. No new toxicity signals were identified. Conclusions: Trametinib did not show promising clinical activity in patients with tumors harboring non-V600 BRAF mutations, and the subprotocol did not meet its primary endpoint.",
author = "Johnson, {Douglas B.} and Fengmin Zhao and Marcus Noel and Riely, {Gregory J.} and Mitchell, {Edith P.} and Wright, {John J.} and Chen, {Helen X.} and Gray, {Robert J.} and Shuli Li and McShane, {Lisa M.} and Rubinstein, {Larry V.} and David Patton and Williams, {P. Mickey} and Hamilton, {Stanly R.} and Conley, {Barbara A.} and Arteaga, {Carlos L.} and Harris, {Lyndsay N.} and O'Dwyer, {Peter J.} and Chen, {Alice P.} and Flaherty, {Keith T.}",
note = "Funding Information: This study was coordinated by the ECOG-ACRIN Cancer Research Group (P.J. O'Dwyer and M.D. Schnall, group co-chairs) and supported by the NCI of the NIH under the following award numbers: CA180820, CA180794, CA233270, CA233230, CA233290, CA233329, CA233180. Funding Information: D.B. Johnson is an employee/paid consultant for Array Biopharma, Bristol-Myers Squibb, Merck, and Novartis, and reports receiving commercial research grants from Bristol-Myers Squibb and Incyte. M. Noel is an employee/paid consultant for and reports receiving speakers bureau honoraria from Celgene. G.J. Riely reports receiving other commercial research support from Novartis, Pfizer, Roche, Takeda, Mirati, and Merck. S.R. Hamilton reports receiving other commercial research support from Guardant Health. C.L. Arteaga is an employee/paid consultant for Novartis, Lilly, Sanofi, TAIHO Oncology, Merck, Daiichi Sankyo, Immunomedics, OrigiMed, Petra Pharma, and Athenex; reports receiving commercial research grants from Pfizer, Lilly, Takeda, RADIUS, and Bayer; and holds ownership interest (including patents) in Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = apr,
day = "15",
doi = "10.1158/1078-0432.CCR-19-3443",
language = "English (US)",
volume = "26",
pages = "1812--1819",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "8",
}