Summary

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• This summary is based on the review of 12 systematic review(s)/meta-analysis(es). ^[1-12]
• In high-risk resected melanoma, vemurafenib demonstrated a recurrence-free survival (RFS) benefit over placebo, but combination therapies like nivolumab + ipilimumab showed the greatest improvement in RFS. Dabrafenib plus trametinib had the lowest hazards for relapse-free survival compared to other treatments, excluding nivolumab regarding overall survival.
• For BRAF-mutated melanoma patients with brain metastases, BRAF inhibitors (vemurafenib and dabrafenib) and the BRAF/MEK inhibitor combination (dabrafenib and trametinib) achieved a significantly higher intracranial disease control (odds ratio 0.58) in previously treated patients versus treatment-naive individuals.
• In hairy cell leukemia (HCL), vemurafenib monotherapy achieved an overall response rate (ORR) of 100% in the US cohort and 96% in the Italian cohort, while the combination of vemurafenib and rituximab resulted in a complete response rate of 100%.
• A meta-analysis indicated that BRAF inhibitors and BRAF/MEK combinations led to improved progression-free survival (PFS) in BRAF-mutant melanoma patients previously treated for brain metastases, with a hazard ratio of 1.22.
• Vemurafenib was associated with an increased risk of grade 3-5 adverse events compared to placebo/observation, while in BRAF-mutated melanoma patients with brain metastases, no significant increase in overall adverse events, grade 3/4 adverse events, and severe adverse events was observed between pre-treated and treatment-naive cohorts using BRAF inhibitors.
• Combined BRAF plus MEK inhibitors had slightly worse gastrointestinal toxicity profiles but better dermatological profiles compared to vemurafenib monotherapy, and vemurafenib was generally well-tolerated across multiple studies, despite a long list of side effects noted in the treatment of Erdheim-Chester disease (ECD).
• Nivolumab and pembrolizumab were associated with lower risks of high-grade adverse events compared to vemurafenib and combination therapies, with pembrolizumab and nivolumab demonstrating the highest probabilities of being less associated with any and grade 3-4 adverse events.
• The reviewed evidence indicates that BRAF mutation status significantly impacts treatment effectiveness, particularly for progression-free survival (PFS) and recurrence-free survival (RFS), with BRAF-mutant patients showing improved outcomes, such as those with BRAFv600K mutations who experienced enhanced PFS with dabrafenib; however, patient age did not significantly influence outcomes.