Phase 3 SELECT Trial Overview

Marcia Brose, MD: Differentiated thyroid cancer historically has been treated by mostly surgery and radioactive iodine. It was usually cured, and in most cases it still is cured, by those 2 modalities. However, there’s about 10% to 15% of patients in whom even after surgery and radioactive iodine the tumor may recur. In those cases, if radioactive iodine is no longer taken up by the tumor or the tumor has grown anyway, other options were needed.

Starting in about 2012 we had the first access to the kinase inhibitor sorafenib. Shortly after that, in 2014, the kinase inhibitor lenvatinib was approved. Both of these are multikinase inhibitors and provided patients with significant progression-free survival for the first time, giving patients a systemic option for treating their cancer.

The phase 3 SELECT trial was a randomized placebo-controlled trial comparing lenvatinib with placebo in patients with differentiated thyroid cancer that was no longer responsive to radioactive iodine who also were not candidates for curative surgery.

This trial was a watershed trial for getting the approval of lenvatinib, both in the United States and in the European Union, as well as other places globally. The patient selection was any patient who was radioactive iodine refractory, but they also have to have progressing disease within the prior 13 months or so.

When we looked at the comparator between placebo or the patients who got lenvatinib, randomization was 2:1, the patients who received lenvatinib were significantly more likely to have a longer progression-free survival than the patients on the placebo arm. The placebo arm patients had a progression-free survival of about 3.8 months, whereas the patients who were on lenvatinib had a progression-free survival of 18 months. This is quite significant as far as patients and patient care goes, and it was the basis for the approval of lenvatinib at that time.

In addition, we also saw very significant overall response rates of 62% and an overall survival that was not actually reached in the original trial. However, subsequent data that we found looking at analysis later on, showed that in the subgroup of patients who were over 65 and had received lenvatinib were statistically living significantly longer than patients who had been assigned the placebo group.

This is 1 of the first times that overall survival seemed to be extended in patients with different differentiated thyroid cancer on any kind of inhibitor therapy.

Transcript edited for clarity.