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Brose Discusses Lenvatinib's Lasting Impact in Treatment of Thyroid Cancer

Gina Columbus @ginacolumbusonc
Published: Monday, Jul 11, 2016

Marcia S. Brose, MD, PhD

Marcia S. Brose, MD, PhD

Patients with progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer treated with lenvatinib (Lenvima) were found to have a significant duration of overall response (DOR), according to updated findings of the SELECT trial presented at the 2016 ASCO Annual Meeting.1

The new efficacy data show that at cut-off, the median progression-free survival (PFS) was 19.4 months for lenvatinib (95% CI, 14.8-29.3) and 3.7 months (95% CI, 3.5-5.4) for placebo (HR, 0.24; 99% CI, 0.17-0.35; P <.0001).

In the 157 patients who received lenvatinib, the median DOR was 30 months (95% CI 18.4-35.2). This was similar across subgroups, except in patients with greater disease burden and those with liver metastases.

Earlier findings of the phase III trial showed that treatment with the multikinase inhibitor reduced the risk of disease progression by 79% (HR, 0.21; 99% CI, 0.14-0.31; P <.001). These results led to the FDA approval of lenvatinib for this indication in February 2015, creating another option for patients alongside the tyrosine kinase inhibitor sorafenib (Nexavar) for the first- or second-line setting.

Nevertheless, the 2 therapies have proven to be fairly comparable—and encouraging—in their results.

“Patients really have 2 options and, because of this, they are probably living longer based on the overall survival data in the 65-and-older group, and they are getting a benefit longer than they ever have before,” says Marcia S. Brose, MD, PhD. “The thyroid cancer patients who are getting diagnosed now are doing much better than the patients who are RAI-refractory even 10 years ago. Every option that we develop is basically another plus for patients.”

In an interview with OncLive, Brose, an associate professor of Otorhinolaryngology, Head and Neck Surgery, at the Hospital of the University of Pennsylvania, discusses the updated SELECT findings, how practitioners are treating patients with lenvatinib, how its use compares with sorafenib, and the challenges that still exist with both therapies for patients with thyroid cancer.

OncLive: How do you find that practitioners are using lenvatinib in comparison with sorafenib?

Brose: It is interesting how much both are being used. I find that people are giving the agent that they feel most comfortable with first. There are some people who have a lot of experience with sorafenib and are going ahead and using it as their first-line choice, also because it was FDA approved first. There are other people who like the data on lenvatinib and are using that as their first line.

At the end of the day, most patients are getting both. The only difference is, really, which one that practitioners give first. Many of these patients, when they start to fail one therapy, are more than healthy and are able to go on to a second-line agent.

The bottom line for lenvatinib—since it has become approved—is that it is being used, probably, for all patients. Everyone is getting both lenvatinib and sorafenib.

What is the optimal sequencing strategy with lenvatinib and sorafenib?

The correct answer for that is that we don’t have an answer, because we don’t have a sequencing study. There were enough differences in the population of the SELECT trial, where the patients were clearly more aggressive. It is impossible to compare the data because it is not apples to apples.

The answer I always give to people is, “It doesn’t matter because everyone is going to get both.” There are reasons why people pick one or the other first—issues that would bias people to choose one over the other is comfort and comorbidity. For instance, lenvatinib has a big issue with hypertension, and people with a lot of cardiac problems who are already on 3 medications are probably not going to get started on that.

For sorafenib, some people may be in manual labor and do a lot of stuff with their hands and feet, and they may choose that they do not want to start with sorafenib. Some patients may need a rapid response, and they may feel that the response with lenvatinib might be a little quicker, so they might start with that. At the end of the day, all patients are getting both. We don’t have an answer to optimal sequencing.

The problem is, patients who are getting sorafenib after lenvatinib may not do as well because the patients who were on the SELECT study initially were already very aggressive. Therefore, some people anecdotally might say, “I don’t give sorafenib after lenvatinib because the patients don’t do well.”


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