Urbonas V, et al. - In a phase 2, randomized, open-label trial, researchers investigated the therapeutic effectiveness of inhibiting mitogen-activated protein kinase pathway by adding kinase inhibitors trametinib or pazopanib to paclitaxel chemotherapy in patients with advanced wild-type BRAF (BRAF-wt) melanoma. A total of 38 patients were randomized to paclitaxel alone, 36 were treated with paclitaxel and trametinib, and 37 with paclitaxel and pazopanib. A maximum of six cycles of paclitaxel and once daily oral administration of 2 mg trametinib and 800 mg pazopanib until disease progression or unacceptable toxicity was administered. An improved progression-free survival and considerably increased objective response rate were achieved with the addition of trametinib to paclitaxel chemotherapy, while no effect was seen on overall survival.