Extending the reach of BRAF-targeted cancer therapy

Paired tumour biopsies established that phosphorylated ERK concentrations decreased after treatment with dabrafenib (83.9% median reduction from baseline, IQR 62.4-89.2) and tumour 18F-fluorodeoxyglucose uptake on PET scans had fallen after 2 weeks (60% median reduction from baseline, 41-70), similar to vemurafenib.2 Importantly, the proportion of patients with Val600Glu BRAFmutant melanoma treated at the recommended phase 2 dose with confirmed objective responses (15 [56%] of 27 patients) was similar to that reported in a phase 3 trial3 of vemurafenib (106 [48%] of 219 patients). Of the ten patients with melanoma and asymptomatic brain metastases, nine had a reduction in size of their brain lesions, including complete resolution in four patients.1 This finding is impressive for two reasons: no previous systemic treatment has shown this degree of clinical activity against melanoma brain metastases, and dabrafenib was not predicted to cross the blood-brain barrier in substantial quantities.