What is the efficacy of Lenvatinib (lenvatinib) 18mg versus 24mg in patients with radioiodine-refractory differentiated thyroid cancer?

From the Guidelines

The recommended starting dose of lenvatinib for patients with radioiodine-refractory differentiated thyroid cancer is 24 mg, as it has been shown to be more effective than the 18 mg dose, with an objective response rate of 57.3% compared to 40.3% in the lower-dose group 1.

Key Points

• The efficacy of lenvatinib is dose-dependent, with higher doses resulting in greater efficacy, as demonstrated by the higher objective response rate in the 24 mg group compared to the 18 mg group 1.
• The safety profile of lenvatinib is comparable between the 18 mg and 24 mg doses, with no significant difference in adverse events 1.
• Individualized treatment decisions should be made based on patient performance status and comorbidities, with the option to reduce the dose to 14 mg, 10 mg, or 8 mg daily if necessary.
• Regular monitoring of blood pressure, thyroid function, electrolytes, and renal function is recommended during therapy with lenvatinib.

Considerations

• Lenvatinib works by inhibiting multiple tyrosine kinases involved in angiogenesis and tumor growth, including VEGFR, FGFR, PDGFR, RET, and KIT.
• Common side effects of lenvatinib include hypertension, diarrhea, fatigue, decreased appetite, and weight loss, which should be monitored regularly.
• The choice of starting dose should be individualized based on the patient's specific needs and medical history, with the goal of maximizing efficacy while minimizing toxicity.

From the FDA Drug Label

1. 2 Pharmacodynamics Exposure-Response Relationships In a multicenter randomized (1:1) double blind trial of 152 patients with radioactive iodine (RAI)-refractory DTC, a dose-response relationship for overall response rate (ORR) was observed over the dose range of 18 mg (0. 75 times the recommended dose of 24 mg) and 24 mg. A higher ORR was observed at the recommended lenvatinib dose.

The study compared 18 mg and 24 mg doses of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer. The results showed a dose-response relationship for overall response rate, with a higher response rate observed at the 24 mg dose compared to the 18 mg dose 2.

From the Research

Study Overview

• The study in question, 3, explores the efficacy and safety of lenvatinib at starting doses of 18 mg/day versus 24 mg/day in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC).
• The primary efficacy endpoint was the objective response rate as of week 24 (ORRwk24), and the primary safety endpoint was the frequency of grade ≥3 treatment-emergent adverse events (TEAEs) as of week 24.

Efficacy and Safety Findings

• The ORRwk24 was 57.3% in the lenvatinib 24-mg arm and 40.3% in the lenvatinib 18-mg arm, with an odds ratio (18/24 mg) of 0.50, indicating that a starting dose of lenvatinib 18 mg/day did not demonstrate noninferiority compared to a starting dose of 24 mg/day.
• The rates of TEAEs grade ≥3 were 61.3% in the lenvatinib 24-mg arm and 57.1% in the lenvatinib 18-mg arm, showing a comparable safety profile between the two doses.

Context and Comparison with Other Studies

• Other studies, such as 4 and 5, have also investigated the use of lenvatinib and other tyrosine kinase inhibitors (e.g., sorafenib) in the treatment of RR-DTC, highlighting the importance of targeted therapies in this patient population.
• A systematic review and economic evaluation, 6, compared the clinical effectiveness and cost-effectiveness of lenvatinib and sorafenib for the treatment of patients with RR-DTC, finding that both treatments result in improved progression-free survival and possibly overall survival, but with significant costs and adverse events.

Treatment Considerations

• The choice of starting dose for lenvatinib in patients with RR-DTC should be based on individual patient factors, including tumor size and growth rate, as well as the potential for adverse events, as discussed in 7 and 5.
• The results of the study, 3, support the continued use of the approved starting dose of lenvatinib 24 mg/day in patients with RR-DTC, with dose adjustments as necessary to manage adverse events.