Combined BRAF and HSP90 Inhibition in Patients with Unresectable BRAF ^V600E-Mutant Melanoma.

ABSTRACT: Purpose: BRAF inhibitors are clinically active in patients with advanced BRAF^V600-mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888.Patients and Methods: Vemurafenib (960 mg p.o. b.i.d.) combined with escalating doses of XL888 (30, 45, 90, or 135 mg p.o. twice weekly) was investigated in 21 patients with advanced BRAF^V600-mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity.Results: Objective responses were observed in 15 of 20 evaluable patients [75%; 95% confidence interval (CI), 51%-91%], wit

SUBMITTER: Eroglu Z 

PROVIDER: S-EPMC6195480 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature