Phase 3 SELECT Trial


A review of the phase 3 SELECT trial examining the use of lenvatinib for the treatment of RAI-refractory DTC and the management of adverse events.

Steven I. Sherman, MD, FACE: The most potent therapy that we have available for treating most patients with radioiodine-refractory DTC [differentiated thyroid cancer] is lenvatinib. This is demonstrated in the phase 3 clinical trial, called the SELECT trial. In this trial was a randomized double-blind study with patients randomized to either lenvatinib or a placebo, as there was no approved standard of care available at that time. The patients were able to cross over from placebo to lenvatinib upon progression, as the primary end point for the study was going to be progression-free survival.

The results were remarkably impressive, with a nearly 5-fold improvement in median progression-free survival from placebo to lenvatinib therapy. Median progression-free survival was about 3½ months for patients randomized to placebo, and over 18 months for patients randomized initially to lenvatinib.

The patients who were included in the SELECT trial were quite representative of the population that we face in the clinic of patients who have had initial surgery. They’ve had radioactive-iodine treatment. They’ve been on TSH [thyroid-stimulating hormone] suppressive thyroid hormone therapy. Many of them were older, over age 60 or 65.

But all of them had demonstrated progression of their disease despite previous radioactive-iodine therapy. Many of the patients had also previously been treated with at least 1 other systemic therapy such as other tyrosine kinase inhibitors.

In the SELECT trial, the most common adverse effects were those that are quite typical of other antiangiogenic tyrosine kinase inhibitors. The most common adverse event that was seen was hypertension, either a new increase in high blood pressure or worsening of high blood pressure for the people who had preexisting hypertension. The management was typically adding or increasing the doses of existing antihypertensive drugs.

Patients responded best to angiotensin-converting enzyme inhibitors, the ARBs, or calcium channel blockers. Because proteinuria was also occasionally seen with some of these patients, the ACE and ARB inhibitors were probably preferred.

Other common adverse effects included diarrhea, which usually was managed symptomatically with drugs like loperamide or tincture of opium; skin rashes were less commonly seen compared with some of the other tyrosine kinase inhibitors; nausea and decreased appetite; and weight loss were also some of the more common ones.

Then finally fatigue, which is actually a rather difficult adverse event to treat. Patients were encouraged to be proactive and to enhance their exercise regimens, to try to maximize their nutrition, and making sure that their thyroid hormone levels remained stable, because lenvatinib therapy could increase their need for thyroid hormone. We didn’t want that to be a contributor to either tumor growth or fatigue.

But some of these can be rather challenging symptoms long-term for patients, particularly the fatigue and weight loss.

Transcript edited for clarity.

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