Unknown

Dataset Information

0

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 that MEK inhibition 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.

SUBMITTER: Johnson DB 

PROVIDER: S-EPMC7165046 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Johnson Douglas B DB   Zhao Fengmin F   Noel Marcus M   Riely Gregory J GJ   Mitchell Edith P EP   Wright John J JJ   Chen Helen X HX   Gray Robert J RJ   Li Shuli S   McShane Lisa M LM   Rubinstein Larry V LV   Patton David D   Williams P Mickey PM   Hamilton Stanly R SR   Conley Barbara A BA   Arteaga Carlos L CL   Harris Lyndsay N LN   O'Dwyer Peter J PJ   Chen Alice P AP   Flaherty Keith T KT  

Clinical cancer research : an official journal of the American Association for Cancer Research 20200110 8


<h4>Purpose</h4>Substantial preclinical evidence and case reports suggest that MEK inhibition is an active approach in tumors with <i>BRAF</i> mutations outside the V600 locus, and in <i>BRAF</i> fusions. Thus, Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in this population.<h4>Patients and methods</h4>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 tre  ...[more]

Similar Datasets

| S-EPMC5796858 | biostudies-literature
| S-EPMC7367548 | biostudies-literature
| S-EPMC4669588 | biostudies-literature
| S-EPMC10309549 | biostudies-literature
| S-EPMC7676884 | biostudies-literature
| S-EPMC7307282 | biostudies-literature
| S-EPMC7774047 | biostudies-literature
| S-EPMC8417872 | biostudies-literature
| S-EPMC10393756 | biostudies-literature
| S-EPMC10906199 | biostudies-literature