What is the role of Lenvima (lenvatinib) in the treatment of Renal Cell Carcinoma (RCC)?

From the Guidelines

Lenvima (lenvatinib) is a recommended treatment option for advanced renal cell carcinoma (RCC), specifically in combination with pembrolizumab as a first-line treatment, based on the results of the CLEAR trial 1.

Key Points

• The combination of lenvatinib and pembrolizumab has shown improved overall survival (OS) and progression-free survival (PFS) compared to sunitinib alone in patients with advanced RCC.
• The recommended dosage is 20 mg of lenvatinib once daily plus 200 mg of pembrolizumab every 3 weeks.
• Lenvatinib works as a multiple receptor tyrosine kinase inhibitor that blocks VEGF receptors and other pathways involved in tumor growth and angiogenesis, while pembrolizumab is a PD-1 inhibitor that enhances the immune response against cancer cells.
• Common side effects include diarrhea, fatigue, decreased appetite, vomiting, hypertension, and decreased weight.
• Blood pressure should be monitored regularly, as hypertension is a common side effect requiring management.
• Thyroid function tests should also be monitored, as thyroid dysfunction can occur.
• Dose modifications may be necessary based on tolerability.

Evidence Summary

The CLEAR trial, a phase III study, compared the efficacy and safety of lenvatinib plus pembrolizumab, lenvatinib plus everolimus, and sunitinib alone in patients with advanced RCC 1. The results showed that lenvatinib plus pembrolizumab significantly improved OS and PFS compared to sunitinib alone. The combination of lenvatinib and everolimus also showed improved PFS, but not OS, compared to sunitinib alone.

Clinical Implications

Based on the evidence, lenvatinib plus pembrolizumab is a recommended first-line treatment option for patients with advanced RCC 1. The combination of lenvatinib and everolimus may be considered as a subsequent therapy option for patients who have received prior anti-angiogenic therapy 1. However, the choice of treatment should be individualized based on patient factors, such as performance status, comorbidities, and prior treatments.

From the FDA Drug Label

1.2 Renal Cell Carcinoma LENVIMA, in combination with pembrolizumab, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). LENVIMA, in combination with everolimus, is indicated for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy.

Lenvima is indicated for the treatment of Renal Cell Carcinoma (RCC) in two scenarios:

• In combination with pembrolizumab for first-line treatment of adult patients with advanced RCC.
• In combination with everolimus for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy 2.

From the Research

Lenvima for RCC

• Lenvatinib, a multitargeted tyrosine kinase inhibitor, has been studied in combination with everolimus for the treatment of advanced renal cell carcinoma (RCC) 3, 4, 5, 6, 7.
• The combination of lenvatinib plus everolimus has shown promising anticancer activity in patients with advanced non-clear cell RCC, with an objective response rate of 26% 3.
• In patients with metastatic RCC, lenvatinib plus everolimus has been shown to improve progression-free survival compared to everolimus alone, with a hazard ratio of 0.40 and an increased objective response rate of 43% 4, 5.
• Lenvatinib plus everolimus has also been studied in patients with primary resistance to front-line targeted therapy or immunotherapy, with some patients achieving partial responses or stable disease 6.
• The CLEAR study, a Phase III trial, is comparing lenvatinib plus everolimus and lenvatinib plus pembrolizumab versus sunitinib monotherapy for first-line treatment of RCC, with primary end points including progression-free survival and objective response rate 7.

Efficacy and Safety

• The efficacy of lenvatinib plus everolimus in patients with advanced RCC has been demonstrated in several studies, with improved progression-free survival and objective response rates compared to monotherapy 4, 5.
• The safety profile of lenvatinib plus everolimus has been shown to be manageable, with common treatment-emergent adverse events including fatigue, diarrhea, decreased appetite, nausea, and vomiting 3, 4.
• The combination of lenvatinib plus everolimus has been approved for the treatment of advanced RCC after one prior antiangiogenic therapy, and is being studied in various clinical trials for its potential use in other settings 4, 5, 7.

Clinical Applications

• Lenvatinib plus everolimus may be a promising choice for second-line treatment of patients with metastatic RCC, particularly those with high disease burden or strongly symptomatic patients 4.
• The combination of lenvatinib plus everolimus may also be effective in patients with primary resistance to front-line targeted therapy or immunotherapy, although further study is needed to confirm this 6.
• Ongoing clinical trials, such as the CLEAR study, will provide further information on the efficacy and safety of lenvatinib plus everolimus in various clinical settings 7.