Dosing of TKI Therapy for RAI-Refractory DTC


A review of a multicenter phase 2 study evaluating the safety and efficacy of lenvatinib starting doses in RAI-refractory DTC.

Steven I. Sherman, MD, FACE: In the SELECT trial, the standard starting dosage was 24 mg daily as a single administration. Many patients, however, eventually required dose reduction, typically at 2 to 3 months after starting therapy because of the difficult-to-manage adverse events. This is not necessarily more common than seen with other tyrosine kinase inhibitors, but it led to the very important question of whether it was necessary to start at 24 mg for all patients.

The experience many had after the drug was approved suggested that perhaps lower doses might be reasonable to start with.

There were recently data presented from a randomized trial to try to address this issue. Patients were randomized to start at either 24 mg of lenvatinib daily or 18 mg.

This was a noninferiority trial, and the primary end point was objective response rate at 24 weeks of therapy. The preliminary results that were recently presented suggested that there was a failure to achieve noninferiority, meaning that the response rate appeared to be higher in patients who started at 24 mg, at about 57%, as compared with about 40% for the patients who started at 18 mg, with only a slight reduction in the frequency of significant adverse events.

Therefore, this trial would suggest that at least for the purpose of achieving tumor shrinkage and a partial response, better outcome would be achieved by starting at the higher standard 24 mg dose.

It is yet to be determined whether progression-free survival and a durable control over tumor growth requires starting at the higher dose or whether starting at a lower dose for patients who don’t need to benefit from objective tumor shrinkage might still be a reasonable compromise.

Transcript edited for clarity.

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