From the Guidelines
The combination of everolimus and lenvatinib is a recommended treatment option for advanced renal cell carcinoma (RCC), offering improved progression-free survival and overall survival compared to single-agent treatments, as evidenced by the most recent study from 2022 1. The benefits of this combination include:
- Improved progression-free survival: The combination significantly extends the time before cancer progresses compared to single-agent treatments.
- Higher objective response rate: More patients experience tumor shrinkage or stabilization with this combination.
- Dual mechanism of action: Everolimus (an mTOR inhibitor) and lenvatinib (a multi-kinase inhibitor) target different pathways involved in cancer growth, providing a more comprehensive approach.
- Option for previously treated patients: This combination is effective in patients who have progressed on prior therapies. Typical dosing is lenvatinib 18 mg orally once daily plus everolimus 5 mg orally once daily, as supported by the study from 2022 1. Some key points to consider when using this combination include:
- Side effects may include fatigue, diarrhea, decreased appetite, and hypertension.
- Regular monitoring of blood pressure, thyroid function, and kidney function is necessary.
- The combination works by simultaneously inhibiting angiogenesis (lenvatinib) and cellular proliferation (everolimus), effectively targeting multiple aspects of tumor growth and survival, as described in the study from 2022 1. The most recent and highest quality study, the CLEAR trial, demonstrated the efficacy of lenvatinib plus everolimus in patients with treatment-naive metastatic RCC, with a median PFS of 14.6 months and an overall response rate of 53.5% 1. Overall, the combination of everolimus and lenvatinib is a valuable treatment option for patients with advanced RCC, offering improved outcomes and a dual mechanism of action, as supported by the most recent evidence from 2022 1.
From the FDA Drug Label
LENVIMA, in combination with everolimus, is indicated for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy. The combination of lenvatinib and everolimus showed increased antiangiogenic and antitumor activity as demonstrated by decreases in human endothelial cell proliferation, tube formation, and VEGF signaling in vitro, and by decreases in tumor volume in mouse xenograft models of human renal cell cancer that were greater than those with either drug alone.
The benefits of everolimus (Rad001) and lenvatinib in Renal Cell Carcinoma (RCC) include:
- Increased antiangiogenic and antitumor activity: The combination of lenvatinib and everolimus has been shown to decrease human endothelial cell proliferation, tube formation, and VEGF signaling in vitro, and to decrease tumor volume in mouse xenograft models of human renal cell cancer.
- Treatment of advanced RCC: Lenvatinib, in combination with everolimus, is indicated for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy. 2 2
From the Research
Benefits of Everolimus (Rad001) and Lenvatinib in Renal Cell Carcinoma (RCC)
The combination of everolimus and lenvatinib has shown promising results in the treatment of advanced renal cell carcinoma (RCC). Some of the benefits of this combination include:
- Improved progression-free survival (PFS) compared to everolimus monotherapy 3, 4
- Increased objective response rate (ORR) compared to everolimus monotherapy 4, 5
- Manageable toxicity profile 6, 5
- Significant gain in quality-adjusted time without symptoms or toxicity (Q-TWiST) compared to everolimus monotherapy 7
Efficacy of Everolimus and Lenvatinib in RCC
The efficacy of everolimus and lenvatinib in RCC has been demonstrated in several studies, including:
- A phase 2 study that showed an ORR of 26% and a median PFS of 9.2 months in patients with advanced non-clear cell RCC 3
- A phase 1b study that showed a partial response rate of 33% and a stable disease rate of 50% in patients with metastatic RCC 6
- A randomized, phase 2 trial that showed an improvement in PFS and ORR compared to everolimus monotherapy 4, 5
Safety Profile of Everolimus and Lenvatinib in RCC
The safety profile of everolimus and lenvatinib in RCC has been evaluated in several studies, including:
- A phase 2 study that showed a manageable toxicity profile, with the most common treatment-emergent adverse events being fatigue, diarrhea, decreased appetite, nausea, and vomiting 3
- A phase 1b study that showed a manageable toxicity profile, with the most common treatment-related adverse events being fatigue, mucosal inflammation, proteinuria, diarrhea, and vomiting 6
- A randomized, phase 2 trial that showed a slightly higher toxicity profile compared to everolimus monotherapy, but still manageable 5