Ngocdiep T. Le

TL;DR: A combination of dabraenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations.

TL;DR: The data show substantial clinical activity of trametinib in melanoma and suggest that MEK is a valid therapeutic target, and differences in response rates according to mutations indicate the importance of mutational analyses in the future.

TL;DR: The recommended phase 2 dose of 2 mg trametinib once a day is tolerable, with manageable side-effects, and its inhibition of the expected target and clinical activity warrants its further development as a monotherapy and in combination.

TL;DR: The response rate for the selective, allosteric MEK1/MEK2 inhibitor trametinib (GSK1120212), in patients with metastatic BRAF-mutant melanoma, and minimal clinical activity was observed as sequential therapy in patients previously treated with a BRAF inhibitor suggest that BRAf-inhibitor resistance mechanisms likely confer resistance to MEK- inhibitor monotherapy.

TL;DR: At RP2D, buparlisib 60 mg + trametinib 1.5 mg daily shows promising antitumor activity for patients with KRAS-mutant ovarian cancer, and long-term tolerability of the combination atRP2D is challenging, due to frequent dose interruptions and reductions for toxicity.