trametinib (Mekinist) is accepted for restricted use within NHSScotland....in combination with dabrafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Among pediatric patients with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy as first-line therapy.

In relapsed/refractory BRAF V600–mutant pHGG, dabrafenib plus trametinib improved ORR versus previous trials of chemotherapy in molecularly unselected patients with pHGG and was associated with durable responses and encouraging survival.

The primary endpoint was met, with an independently assessed ORR of 56.1% (95% CI, 39.7%-71.5%). Median DOR was 22.2 mo (95% CI, 7.6 mo-not estimable [NE]; 12-mo Kaplan-Meier [KM] DOR rate, 62.2%), and median PFS was 9.0 mo (95% CI, 5.3-24.0 mo; 12-mo KM PFS rate, 44.1%). median OS was 32.8 mo (95% CI, 19.2 mo-NE; 12-mo KM OS rate, 76.3%). Treatment with dab + tram demonstrated an improvement in ORR, response durability, and survival compared with estimates based on historical observations with current treatment approaches in r/r BRAF V600–mutant pHGG.

Twenty-eight adults with recurrent or disseminated BRAF V600-mutant gangliogliomas (n=9), pleomorphic xanthoastrocytomas (n=9), and diffuse gliomas...15 combinations of RAFi/MEKi [vemurafenib+cobimetinib (n=5), dabrafenib+trametinib...Eleven patients achieved a partial or complete response (11/28, 39%), with a median reduction of -78% in their tumor burden....Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in two....study highlights the clinical benefits of RAFi/MEKi in adult patients with BRAF-mutant GGNT...