Trametinib activity in patients with solid tumors and lymphomas harboring braf non-V600 mutations or fusions: Results from NCI-MATCH (EAY131)

Douglas B. Johnson, Fengmin Zhao, Marcus Noel, Gregory J. Riely, Edith P. Mitchell, John J. Wright, Helen X. Chen, Robert J. Gray, Shuli Li, Lisa M. McShane, Larry V. Rubinstein, David Patton, P. Mickey Williams, Stanly R. Hamilton, Barbara A. Conley, Carlos L. Arteaga, Lyndsay N. Harris, Peter J. O'Dwyer, Alice P. Chen, Keith T. Flaherty

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1812-1819
Number of pages8
JournalClinical Cancer Research
Volume26
Issue number8
DOIs
StatePublished - Apr 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Johnson, D. B., Zhao, F., Noel, M., Riely, G. J., Mitchell, E. P., Wright, J. J., Chen, H. X., Gray, R. J., Li, S., McShane, L. M., Rubinstein, L. V., Patton, D., Williams, P. M., Hamilton, S. R., Conley, B. A., Arteaga, C. L., Harris, L. N., O'Dwyer, P. J., Chen, A. P., & Flaherty, K. T. (2020). Trametinib activity in patients with solid tumors and lymphomas harboring braf non-V600 mutations or fusions: Results from NCI-MATCH (EAY131). Clinical Cancer Research, 26(8), 1812-1819. https://doi.org/10.1158/1078-0432.CCR-19-3443