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Optimizing Treatment With Lenvatinib in Thyroid Cancer

Insights From: Robert I. Haddad, MD, Dana-Farber; Matthew H. Taylor, MD, Oregon Health;R. Michael Tuttle, MD, MSKCC
Published: Thursday, May 14, 2015
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In the SELECT study, 392 patients with progressive RAI-refractory differentiated thyroid cancer (DTC) were randomized to receive lenvatinib or placebo. The objective response rate with lenvatinib was 64.8% versus 1.5% with placebo. Median progression-free survival (PFS) was 18.3 months with lenvatinib compared with 3.6 months with placebo (P < .001).

Improvements in PFS were observed even after dose reduction or interruption due to toxicities, notes Matthew H. Taylor, MD. Additionally, he notes that patients taking lenvatinib for over 3 years on doses as low as 14 mg continue to respond well.

The starting dose in the SELECT trial was 24 mg, based on the maximum tolerated dose (MTD) determined in phase I dosing trials. The MTD does not equate to being the most efficacious, Taylor adds; consequently, for patients experiencing side effects that are unmanageable or that reduce quality of life, it is reasonable to dose-reduce as long as response continues.
 
While starting patients at the MTD of 24 mg is best, some patients may find this dose intolerable and require incremental dose reductions. Lenvatinib can be effectively stopped while side effects subside and then reinitiated at the next-lowest dose of 20 mg, Taylor notes. If this is tolerated, patients can remain at the 20-mg dose or eventually re-escalate to 24 mg. However, if patients are unable to tolerate 20 mg, Taylor suggests that the dose can be further reduced to 14 mg in order to ensure that patients remain on the therapy.
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For High-Definition, Click
In the SELECT study, 392 patients with progressive RAI-refractory differentiated thyroid cancer (DTC) were randomized to receive lenvatinib or placebo. The objective response rate with lenvatinib was 64.8% versus 1.5% with placebo. Median progression-free survival (PFS) was 18.3 months with lenvatinib compared with 3.6 months with placebo (P < .001).

Improvements in PFS were observed even after dose reduction or interruption due to toxicities, notes Matthew H. Taylor, MD. Additionally, he notes that patients taking lenvatinib for over 3 years on doses as low as 14 mg continue to respond well.

The starting dose in the SELECT trial was 24 mg, based on the maximum tolerated dose (MTD) determined in phase I dosing trials. The MTD does not equate to being the most efficacious, Taylor adds; consequently, for patients experiencing side effects that are unmanageable or that reduce quality of life, it is reasonable to dose-reduce as long as response continues.
 
While starting patients at the MTD of 24 mg is best, some patients may find this dose intolerable and require incremental dose reductions. Lenvatinib can be effectively stopped while side effects subside and then reinitiated at the next-lowest dose of 20 mg, Taylor notes. If this is tolerated, patients can remain at the 20-mg dose or eventually re-escalate to 24 mg. However, if patients are unable to tolerate 20 mg, Taylor suggests that the dose can be further reduced to 14 mg in order to ensure that patients remain on the therapy.
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