RET Inhibitors in Development



Robert Doebele, MD, PhD: If you look in the NCCN [National Comprehensive Cancer Center] guidelines, there are 2 multikinase inhibitors that are suggested.Those are vandetanib and cabozantinib.And we know that those drugs, in general, have relatively low activity, so response rates, perhaps, in the 15% to 20% range, progression free survival only in the few months.And again, this is because they're not able to be dosed appropriately because of adverse effects.

When we look at the selective RET inhibitors that are emerging from clinical trials, selpercatinib and pralsetinib, we're really see far more meaningful activity, response rates much closer to what we expect from a good targeted therapy like we see with EGFR and ALK inhibitors.So, objective response rates in excess of 60%, progression free survival rates that are a year or more.And some of this data is still emerging, so we don't have pics numbers yet.

But it's very clear, even from the early data analysis from both of these new and exciting selective RET inhibitors that were seeing far better efficacy in terms of objective response rate, progression free survival and also importantly intracranial activity.That's not something that we talked about yet.Patients with lung cancer often have very high brain metastasis at diagnosis or will develop them later.

And so having meaningful intracranial activity, meaning the drug penetrates into the bright and can cause tumor shrinkage and tumor control is really critical.And I think we're seeing that from these new selective agents and that is really exciting for our patients.And so again, what we think about the older multikinase agents versus these new selective RET inhibitors, we see far better efficacy and again, with far fewer toxicity.And so that's really what we want for our patients.

Transcript Edited for Clarity

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