Summary

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• This summary is based on the review of 23 systematic review(s)/meta-analysis(es). ^[1-25]
• Overall Response Rates (ORR): Dabrafenib + Trametinib demonstrated significant effectiveness with an ORR of 69.9% in the intention-to-treat (ITT) population, increasing to 87.2% in the 2L population, while Encorafenib + Binimetinib showed a higher ORR of 1.86 (95% credible interval (CrI) 1.10, 3.17) compared to Dabrafenib + Trametinib.
• Progression-Free Survival (PFS): Dabrafenib + Trametinib improved PFS compared to historical treatments, achieving a one-year PFS rate of 55.1% in the ITT population and 74.0% in the 2L population; this regimen was significantly outperformed by Nivolumab + Ipilimumab, which had an hazard ratio (HR) of 0.53 (95% confidence interval (CI), 0.39-0.73) for overall survival (OS) after 12 months.
• Complete Response (CR) Rates: The CR rate for Dabrafenib + Trametinib was 12.1% in the ITT population and 29.7% in the 2L population, highlighting its effectiveness particularly in earlier treatment stages.
• The v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) Mutation Status and Age Impact: Patients with BRAF mutations had a higher recurrence-free survival (RFS) benefit (HR 0.30; 95% CI = 0.11-0.78) compared to wild-type (HR 0.60; 95% CI = 0.44-0.81), while age did not significantly influence treatment outcomes across groups, with similar effectiveness observed in patients aged >65 and <65.
• Adverse Events (AEs): Dabrafenib + Trametinib was associated with common adverse events, including rash, cutaneous squamous-cell carcinoma (cSCC) (lower incidence compared to Dabrafenib monotherapy, relative risk (RR) 0.40; 95% CI 0.18 to 0.89), alopecia, keratoacanthoma (KA), hyperkeratosis (HK), and pruritus, with a higher rate of AEs noted in combination with trametinib compared to monotherapy.
• Severe Adverse Events (SAEs): The combination of Dabrafenib + Trametinib reported a high incidence of grade 3-4 adverse events, while combination therapies like Nivolumab + Ipilimumab were linked to increased SAEs; however, Dabrafenib showed better acceptability for severe AEs compared to Vemurafenib and Encorafenib.
• Discontinuation Rates: Dabrafenib + Trametinib had lower discontinuation rates due to AEs (<1%) compared to Vemurafenib + Cobimetinib, indicating a comparable safety profile to other targeted therapies like Encorafenib + Binimetinib.
• BRAF-Mutant Melanoma: Targeted therapies like Dabrafenib + Trametinib showed higher efficacy and safety profiles, achieving significant improvements in outcomes for patients with BRAF V600 mutations, with notable benefits in RFS and OS.
• Age Groups: No significant age-related differences in treatment outcomes were observed across various age groups, indicating that adjuvant therapy benefits are consistent for older (>65: HR 0.50; 95% CI= 0.36-0.70) and younger (<65: HR 0.58; 95% CI= 0.46-0.75) patients.
• Stage III and IV Melanoma: Combination therapies demonstrated substantial improvements in RFS and OS for high-risk resected and metastatic stages, with stage IIIA patients benefiting equally from adjuvant treatments compared to those with stage IIIB/C.