Summary

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• This summary is based on the review of seven systematic review(s)/meta-analysis(es). ^[1-7]
• Progression-Free Survival (PFS) and Overall Response Rate (ORR): Cobimetinib combined with vemurafenib and atezolizumab demonstrated superior PFS (hazard ratio (HR) = 0.56 [95% CI 0.37-0.84]) and ORR (risk ratio (RR) = 3.07 [95% confidence interval (CI) 1.61-5.85]) compared to ipilimumab/nivolumab, with similar efficacy outcomes reported when cobimetinib/vemurafenib was compared to dabrafenib/trametinib and encorafenib/binimetinib.
• Overall Survival (OS) in BRAF-V600 Mutations: In patients with BRAF(V600)-mutated metastatic melanoma, dabrafenib-trametinib treatment showed a favorable effect on OS compared to vemurafenib-cobimetinib, highlighting a beneficial outcome in this subgroup. Additionally, for patients experiencing progression post-cobimetinib and vemurafenib treatment, subsequent therapies improved post-progression overall survival (ppOS).
• Effectiveness in Subpopulations with Prognostic Factors: In patients treated with cobimetinib and vemurafenib, higher baseline lactate dehydrogenase (LDH) levels (>2 x upper limit of normal) were associated with the shortest ppOS, identifying a prognostic factor that may inform treatment considerations in specific subgroups.
• Grade ≥3 Treatment-Related Adverse Events (TRAEs): Cobimetinib combined in triplet therapy with vemurafenib and atezolizumab trended toward a lower risk of Grade ≥3 TRAEs when compared to ipilimumab/nivolumab (RR = 0.71 [95% CI 0.30-1.67]).
• Serious Adverse Events (SAEs) and Discontinuations: Encorafenib plus binimetinib, when compared to vemurafenib plus cobimetinib, was associated with fewer SAEs and lower discontinuation rates due to adverse events, suggesting a potentially favorable safety profile for patients undergoing combination therapy with encorafenib and binimetinib.
• Baseline factors such as LDH levels greater than twice the upper limit, advanced disease stage, and poor performance status were identified as significant prognostic indicators for shorter ppOS in patients treated with cobimetinib and vemurafenib.