Case Studies in Thyroid Cancer - Episode 18

Selpercatinib: Clinical Practice Implications

The panel of experts discuss practical considerations regarding selpercatinib and the LIBRETTO-001 and LIBRETTO-531 clinical trial data.

Lori Worth, MD: Let me ask very quickly: Andrew and Marcia, what stands out to you about the selpercatinib data?

Andrew Gianoukakis, MD: Efficacy and low adverse-effect profile.

Marcia Brose, MD: I agree. The response rates, newly seen complete responses, and the duration of these responses are incredible and encouraging.

Lori Wirth, MD: Would you say that these data are practice changing?

Andrew Gianoukakis, MD: Yes.

Marcia Brose, MD: Yeah.

Lori Wirth, MD: Great, a new standard of care for people with MTC [medullary thyroid cancer]. Are there any important implications from the LIBRETTO data on our understanding of RET, and the role of RET-targeted therapies in this setting?

Marcia Brose, MD: It confirms what we already know, which is that RET is a driver mutation, and if you take it out, you can get a good response. If you can do that cleanly, then you can decrease the adverse-effect profiles. The implication is that we’re seeing across many tumor types, and it’s nice to see it in this setting.

Lori Wirth, MD: We initially worried that because vandetanib and cabozantinib have good VEGFR inhibition, does that contribute to the efficacy in those drugs? If we take it away in these RET-specific inhibitors, are we still going to see activity? We’re all lucky that the answer is yes, you still see activity. Andrew, say you have a patient who’s kicking along, who’s doing OK, who’s been on cabozantinib for 5 years with RET-mutant MTC. Are you going to stop cabozantinib and switch them to a RET-specific inhibitor?

Andrew Gianoukakis, MD: In this case that the patient is progressing, and it’s time to turn to a new agent. Clearly if they’re RET-positive, you can turn to pralsetinib or selpercatinib. The data are similar for a primary vs secondary use. The answer is yes.

Lori Wirth, MD: My question was, if you have a patient who’s doing well on cabozantinib with disease control, they’re not progressing.

Andrew Gianoukakis, MD: The question that was written said the patient is progressing. But if you change the question, then it could be considered in the case if the drug is toxic for the patient and you haven’t been able to achieve a dose reduction that leads to good quality of life and disease control. It’s reasonable to consider there may be a risk of losing control of the disease. But based on what we know from the trials in the second-line setting, these drugs are nearly equally efficacious as in the primary setting.

This transcript has been edited for clarity.