The SELECT Trial and Differentiated Thyroid Cancer - Episode 5

Post Hoc Analysis of Patients With Lung Metastases from the SELECT Trial

Lori Wirth, MD, reviews key efficacy data from the post hoc analysis of the SELECT trial investigating the use of lenvatinib in patients with lung metastases.

Lori Wirth, MD: For the SELECT trial we’ve done several post hoc subset analyses taking a look at various aspects of the patients enrolled in the trial to try to tease out where there’s the most benefit for patients with lenvatinib. For 1 of the post hoc analyses, we looked at how patients with lung metastases do when they’re randomized to lenvatinib vs placebo in the SELECT trial.

Overall, lung metastases are very common in iodine-refractory DTC [differentiated thyroid cancer], whether we’re talking about papillary, Hürthle cell, poorly differentiated, or follicular thyroid cancer. In the SELECT trial, approximately 90% of patients who were enrolled had lung metastases. In the post hoc subanalyses, we took a look at the patients with lung metastases and then broke down the patients into various groups: lung metastases that were 1 cm or larger, 1.5 cm or larger, 2 cm or larger, etc.

We then looked at how these various subgroups of patients with lung metastases did. Perhaps not unsurprising, we found that when patients had lower-volume disease, they seemed to do better in terms of progression-free survival when they were randomized to lenvatinib compared with placebo; that’s not unexpected. One of the things that I was surprised by the data was that we looked at overall survival as well, and found that there was an overall survival benefit in patients with lung metastases that were even as small as 1 cm, even though 88% of the patients who were initially randomized to placebo crossed over at progression and received lenvatinib.

In that group of patients with iodine-refractory progressive DTC who had lung metastases that were as small as 1 cm, when they were randomized to lenvatinib they had a median overall survival of 44.7 months vs 33.2 months when they were randomized to placebo, even though most of the placebo patients progressed and then crossed over and received lenvatinib. To me, that means we need to think about this potential overall survival benefit for patients with lung metastases, particularly when we’re thinking about when to start therapy.

If overall survival is the most important thing to a patient with DTC iodine-refractory that’s progressive, and they have lung metastases, the patient wants to live longest. That’s the most important thing to them, so perhaps starting earlier is going to be better for that patient than holding off and waiting as long as possible before starting lenvatinib, in order to put off the time that they would experience the side effects with lenvatinib therapy. It is on the basis of these data and some other similar data that suggest that efficacy benefits with lenvatinib are best when you start earlier in the disease process rather than holding off and starting later and later.

Lung metastases are very common in patients with iodine-refractory DTC; we see lung metastases in most patients. A very typical pattern for patients with papillary thyroid cancer is a shower of small lung metastases. We can see lung metastases in follicular thyroid cancer, Hürthle cell, and poorly differentiated thyroid cancers as well. With follicular thyroid cancer, we also tend to see bone metastases more frequently than we see bone metastases in patients with papillary thyroid cancer. Across all the subtypes, lung metastases are very common. With disease progression, patients with lung metastases can develop shortness of breath, dyspnea, and cough or bronchial obstruction. Another thing we see, which is somewhat characteristic of patients with thyroid cancer and lung metastasis, is hemoptysis. There tends to be a lot of angiogenesis in these tumors and neovasculature; when they invade the bronchi, patients tend to develop hemoptysis.

Transcript edited for clarity.