Summary

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• This summary is based on the review of 19 systematic review(s)/meta-analysis(es). ^[1-19]
• Renal Cell Carcinoma (RCC): Lenvatinib combined with Everolimus ranked highest in effectiveness, showing superior overall survival (OS) (hazard ratio (HR) = 0.44; 95% confidence interval (CI) = 0.24-0.82), progression-free survival (PFS) (HR = 0.13; 95% CI = 0.07-0.24), and objective response rate (ORR) (odds ratio (OR) = 35.95; 95% CI = 11.55-111.87) compared to placebo. Cabozantinib ranked second in OS (HR = 0.57) and PFS (HR = 0.19), while Nivolumab had the lowest risk of severe adverse events (SAE).
• Tuberous Sclerosis Complex (TSC): Oral Everolimus demonstrated significant effectiveness in reducing renal angiomyolipoma size by 50% (relative risk (RR) = 24.69; P = 0.001), reducing subependymal giant cell astrocytoma (SEGA) tumor size by 50% (RR = 27.85; P = 0.02), and decreasing seizure frequency by 25% and 50% (P = 0.0001 and P = 0.0004, respectively). It also showed notable improvement in skin responses (RR = 5.78; P = 0.0002).
• Neuroendocrine Tumors (NETs): Everolimus and Sirolimus effectively stabilized lung function and reduced angiomyolipomas in patients with lymphangioleiomyomatosis (LAM), with Everolimus also enhancing PFS and OS in patients with metastatic NETs, highlighting its clinical benefit in these conditions.
• RCC: The combination of Everolimus with Lenvatinib was associated with a higher risk of severe adverse events (SAEs) compared to other treatments, necessitating frequent dose adjustments, interruptions, or withdrawals due to adverse effects. Nivolumab presented the lowest incidence of SAEs among the RCC treatments.
• Tuberous Sclerosis Complex (TSC): While overall adverse events were similar between Everolimus and placebo, patients on Everolimus experienced more severe adverse events, leading to increased treatment modifications.
• NETs: Everolimus and Sirolimus were generally well-tolerated with primarily mild side effects, although Everolimus showed a higher rate of severe adverse events compared to placebo.
• Population studies included previously treated adolescents and adults with metastatic RCC, NETs, and TSC, with age ranges spanning from 3 months to 65 years for TSC. Subgroup analyses identified no significant differences in adverse events between children and adults with TSC and showed that RCC patients with higher mTOR inhibitor levels had increased discontinuation rates due to adverse effects.