Combined BRAF, MEK, and heat-shock protein 90 (HSP90) inhibition in advanced BRAF V600-mutant melanoma.

Combined vemurafenib and cobimetinib plus XL888 had significant toxicity, requiring frequent dose reductions, which may have contributed to the relatively low progression-free survival despite a high tumor response rate. Given overlapping toxicities, caution must be used when combining HSP90 inhibitors with BRAF and MEK inhibitors.