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Intermittent vs Continuous Dosing of Dabrafenib Plus Trametinib in Advanced Melanoma

By: Jenna Carter, PhD
Posted: Friday, February 23, 2024

Studies have reported success with BRAF and MEK inhibitors in extending the life expectancy of patients with BRAF V600–mutant advanced melanoma; however, as treatment progresses, most patients develop resistance. An article published in the European Journal of Cancer reported findings from the INTERIM phase II study, which examined the impact of intermittent dosing on the efficacy of BRAF and MEK inhibitors in patients with this type of skin cancer. Pippa Corrie, PhD, FRCP, of the Cambridge University Hospitals NHS Foundation Trust, United Kingdom, and colleagues ultimately reported no differences in efficacy between the continuous- and intermittent-dosing groups.

“[Continuous] daily dosing of oral kinase inhibitors may promote clonal expansion of drug-resistant cells, and intermittent drug dosing was proposed as a strategy to delay the onset of disease progression,” explained the investigators.

To assess treatment efficacy, a total of 79 patients were recruited (n = 39 intermittent, n = 40 continuous) for this study. All patients were diagnosed with BRAF V600–mutant advanced melanoma and were randomly assigned to receive either continuous (daily dabrafenib plus trametinib) or intermittent (dabrafenib on days 1–21, trametinib on days 1–14 every 28 days) doses.

Findings revealed the median progression-free survival was 8.5 months (intermittent) vs 10.7 months (continuous; hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 0.79–2.45 months, P = .255). The median overall survival was 18.1 months in the intermittent arm vs not reached in the continuous arm (HR = 1.69, 95% CI = 0.87–3.28 months, P = .121). Additional findings revealed an objective response rate of 57% (intermittent) vs 77% (continuous). However, patients in the intermittent group reported fewer treatment-related adverse events (76% vs 88%) but more grade 3 or greater events. Overall, the authors concluded that intermittent dosing did not offer a benefit in all measures of efficacy.

Disclosure: The study authors reported no conflicts of interest.

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