Advances from the LIBRETTO Program in Thyroid Cancer


Marcia S. Brose, MD, PhD, FASCO, discusses trials LIBRETTO program leading up to LIBRETTO-531.

Marcia S. Brose, MD, PhD, FASCO, professor in the Department of Medical Oncology Sidney Kimmel Medical College Thomas Jefferson University, professor and vice chair in the Department of Medical Oncology Jefferson Northeast, chief of Cancer Services, Sidney Kimmel Cancer Center-Jefferson Northeast, associate director of Community Based Clinical Research, and SKCC chair of Hematology/Oncology, Jefferson Torresdale Hospital, discusses trials LIBRETTO program leading up to LIBRETTO-531 (NCT04211337).


0:08 | There are 2 types of thyroid cancer actually have alterations in the gene called RET medullary thyroid cancer, they're actually quite common, and can be in over 50%. And those are usually point mutations. Half of those patients may have it because it was hereditary and the other half had, what's called ‘sporadic just showed up in the cancer.’ There's another up to 20% of patients in differentiated thyroid cancer who have RET fusions. In both medullary thyroid cancer, the point mutations and the fusions with differentiated thyroid cancer, RET can be upregulated.

0:45 | In the first trial, which was LIBRETTO-001. We basically looked at both groups and show that if we use the selective RET inhibitor selpercatinib, we got very nice responses, patients were able to maintain their responses for extended periods of time. We already had other agents approved for medullary thyroid cancer and differentiate thyroid cancer, they're called multi kinase inhibitors, right? They're a little less specific, their primary activity is VEGF receptor inhibition, but they also hit RET. And the question was, well, if we have a very selective inhibitor, is that better? Is it better to start with that or the multikinase inhibitors?

1:36 | We only knew kind of anecdotally, from the LIBRETTO-001 trial that these seem to be fairly well-tolerated. And, you know, selpercatinib still has side effects, but it didn't seem to be quite to the degree that we had seen with some of the multikinase inhibitors like either cabozantinib [Cabometyx] and vanndetanib [Caprelsa].

1:57 | In the case of medullary thyroid cancer or lenvatinib [Lenvima], sorafenib [Nexavar], and now cabozantinib, in the case of differentiated thyroid cancer. So then the question became, are we better off being really selective or not?

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