Although previous studies suggest objective responses with BRAF and MEK inhibitors in the majority of patients with BRAF-mutant melanoma, data also suggest that acquired resistance limits response durations with these drugs. Preclinical data suggest that intermittent dosing of these agents may delay such resistance. To determine whether intermittent dosing of BRAF/MEK inhibitors improved progression-free survival (PFS) in patients with advance BRAF-mutant melanoma when compared with continuous dosing, researchers randomized patients on 8-weeks of continuous BRAF/MEK inhibitor therapy to either further continuous therapy or intermittent dosing on a 3-week-off, 5-week-on schedule. Median PFS was statistically significantly longer (9 months from randomization) with continuous dosing when compared with intermittent dosing (5.5 months). At a median follow-up of 2 years, median overall survival was 29.2 months in both groups. In the continuous treatment group, 77% of patients discontinued treatment due to disease progression, compared with 84% in the intermittent treatment group.
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