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ASCO 2021 | Phase II trial of lenvatinib for anaplastic thyroid cancer

An unmet need remains for effective therapeutic options in anaplastic thyroid cancer where prognosis is poor. Marcia Brose, MD, PhD, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, talks on the findings of a Phase II single arm trial (NCT02657369) of lenvatinib for the treatment of patients with anaplastic thyroid cancer. 20 patients were evaluated in a planned interim analysis, where it was demonstrated that the minimum overall response rate threshold of 15% had not been met. Lenvatinib therapy was well tolerated in this patient population, with no major treatment-related bleeding events or grade 5 treatment-related adverse events. Prof. Brose discusses the implications of these findings and the need for further investigation into effective agents for anaplastic thyroid cancer. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.

Transcript (edited for clarity)

We studied anaplastic thyroid cancer and the possibility of using lenvatinib as an agent. We had seen sometimes that patients had responses and we really wanted to understand whether or not lenvatinib would be a good option for these patients. This study was designed with a fairly high bar of trying to find four responses out of the patients in the first 20 patients and unfortunately, it did not meet its primary endpoint...

We studied anaplastic thyroid cancer and the possibility of using lenvatinib as an agent. We had seen sometimes that patients had responses and we really wanted to understand whether or not lenvatinib would be a good option for these patients. This study was designed with a fairly high bar of trying to find four responses out of the patients in the first 20 patients and unfortunately, it did not meet its primary endpoint. So what that tells us is something that we actually were aware of previously, which is that sometimes even a single agent such as a JAK receptor inhibitor is not really enough in anaplastic thyroid cancer.

At this point, we have no real agents approved for all comers. There is dabrafenib and trametinib doublet, which is approved for patients with BRAF mutated anaplastic thyroid cancer, but even that doesn’t last forever. TRK fusions, patients who have TRK fusions in their anaplastic thyroid cancer can also obviously get larotrectinib. But again, these are very, very short-lived.

So while lenvatinib can show some responses and we’ve even seen that with sorafenib and some other ones, what it really tells us is that single agent, these are very, very short-lived responses. So we really need to find other agents that we can bring to bear to have a more prolonged response, because anaplastic thyroid cancer, even with the dabrafenib, trametinib story, that only treats the third of patients that have BRAF mutations. We still have a long way to go in anaplastic thyroid cancer, and we need more research.

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