Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131)

Substantial preclinical evidence and case reports suggest that MEK inhibition is an active approach in tumors with mutations outside the V600 locus, and in fusions. Thus, Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in this population. The NCI-MATCH study performed genomi...

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Veröffentlicht in:Clinical cancer research 2020-04, Vol.26 (8), p.1812-1819
Hauptverfasser: Johnson, Douglas B, Zhao, Fengmin, Noel, Marcus, Riely, Gregory J, Mitchell, Edith P, Wright, John J, Chen, Helen X, Gray, Robert J, Li, Shuli, McShane, Lisa M, Rubinstein, Larry V, Patton, David, Williams, P Mickey, Hamilton, Stanly R, Conley, Barbara A, Arteaga, Carlos L, Harris, Lyndsay N, O'Dwyer, Peter J, Chen, Alice P, Flaherty, Keith T
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Sprache:eng
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Zusammenfassung:Substantial preclinical evidence and case reports suggest that MEK inhibition is an active approach in tumors with mutations outside the V600 locus, and in fusions. Thus, Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in this population. 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 were assigned to Subprotocol R using the NCI-MATCHBOX algorithm. The primary endpoint was objective response rate (ORR). Among 50 patients assigned, 32 were eligible and received therapy with trametinib. Of these, 1 had a fusion and 31 had 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 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 ( = 8) had particularly poor PFS. No new toxicity signals were identified. Trametinib did not show promising clinical activity in patients with tumors harboring non-V600 mutations, and the subprotocol did not meet its primary endpoint.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-19-3443