TRK Inhibitors: A Tumor Agnostic Approach to Treatment of Solid Tumors - Episode 12
David Hong, MD:Marcia, you’re 1 of the world experts in thyroid cancer. Can you just give us an overview of what is the current landscape of treating radioactive iodine [RAI]refractory metastatic thyroid cancer?
Marcia Brose, MD, PhD:Radioactive iodinerefractory cancer has just really started to be treated in the last, say, 10 years. And we’ve had the FDA approval of 2 agents: sorafenib and lenvatinib. Both of them are active, and both of them produce responses and really prolonged progression-free survival. They’re not easy always to take, and we have to manage adverse effects, but they really have turned it around for many patients who would have otherwise had nothing.
David Hong, MD:When you look at that space right now, what are some of the unmet needs?
Marcia Brose, MD, PhD:I think that the main unmet need is, as wonderful as these 2 drugs are, they don’t last forever. The No. 1 unmet need is that there’s still a need. Now you have a lot of patients who are surviving longer. When they start to get progression, they actually have very good performance status, and they really are candidates for additional therapies.
David Hong, MD:Thyroid is 1 of the fastest-growing cancers in prevalence, right? How many patients who are affected in a year have radioactive iodinerefractory metastatic thyroid?
Marcia Brose, MD, PhD:You know, that’s a really good question, because we don’t really have numbers to say how many. The vast majority of patients will actually be cured of their disease. Much of the growth in the incidents over the last few years has been in the small early detection of diseases that are usually going to be cured. I would say we’re probably between 6000 and less than 10,000 patients newly diagnosed a year who end up with RAI-refractory disease.
David Hong, MD:Given the data from all these studies, a good number of these patients have been thyroid cancer patients. Where do these treatments fit in that context?
Marcia Brose, MD, PhD:That’s a good question, because you could say now that we have these drugs that have very low toxicity. In all cancers, we have an unmet need for therapies that don’t cause adverse effects or are very, very tolerable. On 1 level, we would say there’s an unmet need always for something after the FDA-approved drugs when we’re actually treating people. And so when getting testing for those people, I do it once they’re even on any systemic therapy. I’m getting everybody tested, and it’s not actually just forTRKfusions, because now we have very exciting drugs coming out and they’re actuallyRETfusions as well in RAI-refractory. There are alsoBRAFmutations, and there are very good phase II data for both dabrafenib and vemurafenib.
We’re wanting to get testing now earlier, because often we want to know at the beginning what our choices are. We might sequence these different options based sometimes on this tolerability of them rather than just on how long they last. In general, we use the FDA-approved drugs as first line and second line. That might start to change, because if the adverse-effect profile of these new drugs is much lower or the toxicity is much lower, then they might start to creep in. And many people are starting to think maybe we can try them earlier on.
David Hong, MD:When do you actually start testing, whether it’s NGS [next-generation sequencing] or anything elsemutations, etc.—for these patients? Is it earlier than when you treat them with radioactive iodine or when you first get the tissue?
Marcia Brose, MD, PhD:Interestingly, there are 2 phases of a thyroid cancer patient. When they’re first getting their nodules worked up, sometimes they will have had some sort of a panel done. Often, by the time they come later, we might at least know theBRAFstatus. In my opinion, once a patient is starting to progressthey have RAI-refractory disease—I know they’re going to need systemic therapy. I want to know then what their choices are. If they have aBRAFmutation, then I may not be ordering NGS testing on them right away. Because I know that for the most part, we’re probably not going to find a lot else because they tend to be mutually exclusive. However, in all patients who areBRAF-negative, I definitely will be ordering it, because I want to know what our options are for sequencing purposes.
Transcript edited for clarity.