LIBRETTO Program Makes Strides in Thyroid Cancer

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 the landscape of thyroid cancer by explaining the complexities and promising advancements seen in the space.

Specifically, Brose explains background on the LIBRETTO program and what strides have been made because of the LIBRETTO studies.

Transcription:

0:10 | There are 2 types of thyroid cancer that have alterations in the gene called RET medullary thyroid cancer. They're quite common and can be in over 50%. 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 with 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.

0:48 | In the first trial, which was LIBRETTO-001 [NCT03157128], we looked at both groups and showed that if we use the selective RET inhibitor selpercatinib [Retevmo], 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 differentiated thyroid cancer called multikinase inhibitors. They're a little less specific, their primary activity is VEGF receptor inhibition, but they also hit RET. The question was, if we have a very selective inhibitor, is that better? Is it better to start with that or the multikinase inhibitors?

1:39 | We only knew from the LIBRETTO-001 trial that these seem to be fairly well-tolerated. Selpercatinib still has [adverse] 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]. In the case of medullary thyroid cancer or lenvatinib [Lenvima], sorafenib [Nexavar], and now cabozantinib, in the case of differentiated thyroid cancer. Then the question became, are we better off being selective or not?