Lori Wirth, MD: So, listen, maybe Marcia, you can help us wrap up by helping us think about future directions in advance DTC [differentiated thyroid cancer].

Marcia Brose, MD, PhD, FASCO: I think that there’s a lot of future directions and I think where a lot of them have been mentioned already with upcoming trials where we’re looking at other combinations for RET, RAI [radioactive iodine], redifferentiation. There are definitely multiple studies coming up where either kinase inhibitors are being partnered with each other or with immunotherapy. I think that we definitely have a bad, unmet need in anaplastic thyroid cancer—still haven’t done anything that really has made a big impact with the exception of the BRAF inhibitors—which I do think helps some of those patients with anaplastic. Of course, the third of them that might have BRAF mutations, but two-thirds of them don’t have BRAF mutations and are a huge unmet need. And now although already we’re starting to get unmet need with the patients who have advanced thyroid cancer that have failed the therapies that we have now.

I’m really hopeful that we’ll maybe find more targets that we could hit, that we’ll be able to do these targeted therapies really have been such a joy to work with because the side effect profiles have been lower and the response rates have been so high I think we’re just going to continue to go in these 4 or 5 directions. I think we’re going to get a little bit more data about head-to-head which is the better first-line and what’s a better second-line, which we haven’t really had that much data for. I know that there’s a RET inhibitor study right now that we have going on at our site. Many of you have at your sites randomizing patients to either RET inhibitors upfront versus standard of care or for medullary thyroid cancer, for instance.

We’re going to start to get some of those studies under our belts. They might start to give us more direction where to go in the first-line, because a lot of these phase 2’s you can’t compare really side-to-side to some of the larger studies. It’ll be nice to get some really good, randomized trials to figure out some of the sequencing in the future.

Lori Wirth, MD: Yes. I agree that the selpercatinib [Retevmo] and pralsetinib [Gavreto] randomized trials are so important, not just for their primary end point but also for that other important question about is there a sequence that’s better. If you develop acquired resistance on selpercatinib or pralsetinib, can you still have activity with lenvatinib [Lenvima] or cabozantinib [Cabometyx] and MTC [medullary thyroid cancer]?

Speaking of cabozantinib, I’d asked Naifa, which cabozantinib are we talking about in DTC? So those of us who do thyroid cancer are used to thinking about cabozantinib as Cometriq—the FDA [Food and Drug Administration] approved formulation for medullary thyroid cancer. Naifa, do you want to unmute, say one word about Cometriq versus Cabometyx?

Naifa L. Busaidy, MD, FACP, FACE: Yes. Sorry, I didn’t answer your question, didn’t mean to ignore it. So basically, it can get very confusing because we all use generic names every day and even when we’re writing it out, and the formulations are very different and so they cannot be interchanged. And so, cabozantinib was looked at 60 milligrams a day and that’s under the brand name of Cabometyx. And it’s very different from the cabozantinib under the brand name Cometriq from medullary thyroid cancer where that was 140 milligrams. Now, they’ve completely changed the formulation but they’re not equivalent and we have to be really careful. And that’s even different from kidney cancer for physicians that treat both.

Lori Wirth, MD: Thank you for that point of clarification. Maria and Giuseppe, any other thoughts that you may have in terms of future directions—things that we don’t want to miss, Maria?

Maria E. Cabanillas, MD: Yes. I think a Hurthle cell is a real opportunity. We’ve made great strides in anaplastic thyroid cancer and in differentiated thyroid cancer and medullary thyroid cancer. But Hurthle cell is one of those orphan diseases and it’s a rare type of differentiated thyroid cancer. We didn’t talk much about it today. It does respond well to lenvatinib but we know that we need other therapies because, like I said this is a marathon, [and] at some point we’ve got to switch to something else or a patient can’t tolerate it. I think we have a trial coming up with immunotherapy in Hurthle cell and so that to me is the next frontier.

Giuseppe Barbesino, MD: To me, I said that briefly before, but if I had the genie in a bottle coming out my first wish would be to have a tissue-based test that can tell me who is radioactive iodine sensitive and who is not. I still believe that we treat so many patients in whom the iodine is not effective, and we don’t do a good service to them. And we need really to dissect the molecular biology of the cancer cell and understand who can respond and who doesn’t on the tissue. And I do think that the tools are there because we understand this so much better than we did in the past that we should be able to tell. And I’m hopeful that in the next few years I will sit in front of a patient and look at a report and say, “Well, I don’t think radioactive iodine is a good thing for you. Maybe we can try with redifferentiation but not as it is.” And the other person is, “Oh, wow, you’re a great candidate.” I think if there is any cancer set will be wiped off by the radioactive iodine, that would be my real hope for the future.

Marcia Brose, MD, PhD, FASCO: Can I just say one thing, Lori? I’m sitting here thinking about where we were 10 years ago, and I think that we all have to really be appreciative of the fact that 10 years ago we had nothing approved. There are not a lot of cancer types where such great research, collaboration and advancements have happened. We’ve had now 3 FDA approvals, multiple phase 2’s that are showing activity, and then 3 more targeted therapies also getting FDA approval. I just want to say kudos to the whole thyroid world. I think that the research has really gone and really shown a big difference. And I think that the people who benefit the most are patients from all of these drugs.

Lori Wirth, MD: I think that is a great note to end this program on. I completely agree that the last decade has been a world of progress for our patients. I think that many patients’ lives have really been changed dramatically by all of the hard work that the people have been putting into this work to get new drugs for our patients with thyroid cancer. Listen, let me thank you all for this rich and informative discussion. And I really appreciate your joining me in today’s discussion. Thank you again also to our viewing audience. We hope that you found this OncLive® Peer Exchange discussion to be useful and informative. Good night, everyone.

Marcia Brose, MD, PhD, FASCO: Good night.

Maria E. Cabanillas, MD: Good night.

Naifa L. Busaidy, MD, FACP, FACE: Good night.

Transcript edited for clarity.