Summary

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• Mektovi (binimetinib) is indicated in combination with encorafenib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test; and is indicated in combination with encorafenib for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.
• This summary is based on the review of nine systematic reviews/meta-analyses. ^[1-8]
• Effectiveness in Melanoma: Encorafenib + Binimetinib demonstrated a superior overall response rate (ORR) compared to Dabrafenib + Trametinib (OR = 1.86; 95% CrI 1.10-3.17) and was comparable to Atezolizumab + Vemurafenib + Cobimetinib for other efficacy endpoints. Nivolumab + Ipilimumab showed improved overall survival (OS) compared to Encorafenib + Binimetinib (HR = 0.60; 95% CI 0.42-0.85) and was more effective than BRAF/MEK inhibitors in long-term outcomes.
• Progression-Free Survival (PFS) in Melanoma: Both Encorafenib + Binimetinib and Dabrafenib + Trametinib had similar PFS outcomes, with no statistically significant differences in OS, PFS, or ORR when compared indirectly to other BRAF/MEK inhibitors. Nivolumab + Ipilimumab, however, showed better PFS compared to BRAF/MEK inhibitors after 12 months of treatment.
• Effectiveness in BRAF V600E-Mutant Metastatic Colorectal Cancer (mCRC): Encorafenib combined with Cetuximab, with or without Binimetinib, significantly extended OS compared to irinotecan/FOLFIRI plus cetuximab, highlighting its effectiveness in this specific population.
• Safety Profile: Encorafenib + Binimetinib demonstrated fewer serious adverse events (SAEs) compared to Vemurafenib + Cobimetinib (OR = 0.51; 95% CrI 0.29-0.91) and Atezolizumab + Vemurafenib + Cobimetinib (OR = 0.41; 95% CrI 0.21-0.82). Additionally, there were fewer discontinuations due to adverse events with Encorafenib + Binimetinib compared to Vemurafenib + Cobimetinib (OR = 0.45; 95% CrI 0.21-0.96).
• Comparative Toxicity: Combination BRAF + MEK inhibitors, including Encorafenib + Binimetinib, were associated with a higher risk of cardiovascular adverse events (CVAEs) compared to BRAF inhibitor monotherapy, while immunotherapies generally had better acceptability for adverse events compared to targeted therapies.
• Subgroup Findings: Patients with BRAF V600E/K mutant melanoma and metastatic colorectal cancer (mCRC) were the primary focus, with age-related risks identified, such as a significantly higher risk of decreased left ventricular ejection fraction in patients younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and an increased risk of pulmonary embolism associated with longer follow-up times (mean follow-up >15 months, RR, 7.70; 95% CI, 1.40-42.12; P = .02).