Transcript:R. Michael Tuttle, MD: Frank, if I ask you to think outside the box a little bit, we did the easy stuff, the BRAF, the tyrosine kinase, the immunotherapies. From an oncology perspective, are there other things we need to think about? Are cytotoxics really dead in this disease or combinations? What should we be thinking about?

Frank Worden, MD: Right. It’s interesting, Mike. I think, first of all—like Eric alluded to this and so did you about clinical trials—we should always be thinking clinical trials because we’re never going to be able to answer these questions unless we put people on clinical trials. I definitely want to put a plug in for that. But what do you do when you give patients agents and they progress through both of them, adding mTOR inhibitors like Marcia and Eric have done? The importance of sequencing is definitely needed because we really don’t know what the right sequence is for these drugs, like they have studied, let’s say, in renal cell carcinoma.

In my own experience, I have occasionally used cytotoxic chemotherapy drugs. I’ve found a combination of gemcitabine and docetaxel to be somewhat effective; it’s used in other cancers. But it would have to be in someone who has a very big disease burden who can’t get radiation therapy or management of symptoms, or cannot get a tyrosine kinase inhibitor of any kind; when you petition to the drug company and the insurance isn’t going to cover it. We also have data from our own institution where we—in waiting for upcoming trials with TKIs—talked to the sarcoma people, and they have a nice oral combination of oral Cytoxan and the oral mTOR inhibitor, rapamycin. And because the mTOR pathway is active and the Cytoxan is non-cell—cycle specific, we found some responses, and we actually published our data based on a handful of people. So, there may be a role in that realm, and the nice thing about that combination is it’s very well tolerated. I think there is room for thinking outside the box, but I think we need to exhaust all our standard measures first.

R. Michael Tuttle, MD: Yes, we’ve come a long way. As we finish up here, I want everybody to have at least a couple minutes to just give some closing comments, main teaching points, and main things; something you just want to share before we close. Dr. Sherman.

Eric Sherman, MD: I think the thing that was put out is that, unlike a decade ago, we definitely have drugs that work in thyroid cancer or in metastatic RAI—refractory thyroid cancer. I think we always have to think about when we’re going to start those drugs, and we have to understand how we’re going to, in terms of dosing—and not start a low dose—try to make a person have no side effects. At the same time, you don’t want to have a person on a high dose with a lot of side effects and never make a change. There’s a lot of things that have to be considered when you do it. But still, even though I think that we’re unbelievably light years ahead than we were a decade ago, we need to think about clinical trials and that there is a lot further that we have to go in thyroid cancer.

There’s a lot of interesting drugs that are available, and even thinking about drivers of what’s going on in thyroid cancer cells, we always talk about BRAF and RAS. There are rare mutations out there where there are things called “basket studies” that people can take part in. So, ALK translocations—actually, I haven’t seen one of those—but you definitely have patients out there with it that have responded to ALK inhibitors. There are other mutations that exist for which where there are very interesting studies that are targeting those mutations. And those patients will have opportunities that are beyond their thyroid cancer. So, you always need to think about what else might be available and what are the studies that are going on. And I think you always have to approach the disease that way. R. Michael Tuttle, MD: So, we’re pushing forward. Marcia?

Marcia S. Brose, MD, PhD: I guess I want to add one thing that we haven’t really hit on—and I think it brings together a lot of what we talked about today—is the fact that, building on what Eric said, we are 10 years ahead of where we were 10 years ago, where it was a no-brainer, as Frank said. They came and you said, “I have nothing for you,” or we gave them chemotherapy and you guys all hated us.

R. Michael Tuttle, MD: This is true.

Marcia S. Brose, MD, PhD: So, we’re 10 years away from that, where we now have not one, we have two FDA-approved therapies. But we have probably another 10 clinical trials showing efficacy of other agents, if not 20 at this point. And I think that what we really need to emphasize is that thyroid cancer patients, as much as possible, need to get to a center of excellence because this is a rapidly moving field. There are doctors who, if you’re not really focused on thyroid cancer, you’ll never be able to really offer, I think, what is really becoming cutting-edge. There’s probably about 10 sites across the country where we really focus on these cancers, and since so many of the times we can give them a bottle and they can come back several weeks later after the initial phase-in period…

I have a patient coming from Brazil next week, so it actually is not impossible to have people travel for this. You can partner with a local, even a primary care or an endocrinologist. So, I think that we’re really making such great strides. But if you’re not getting to a Center of Excellence—and I think that if you’re a community doctor who’s dealing with for the first time—don’t deal with it alone. Even seeing somebody at Sloan Kettering Cancer Center, or in Texas, or Michigan, you can get really great input and you can get guidance on how to give these most effectively. Because I think all of us at all the centers are more than happy to help the local community oncologist. But you really want to know that.

R. Michael Tuttle, MD: Very good. Naifa.

Naifa Busaidy, MD, FACP, FACE: I think that we need to do more research. We need more funding in this area to be able to answer the proper questions and start thinking, let’s biopsy these patients at time of progression initially, try and figure out what’s happened to the tumor, what therapy is next, thinking about sequential therapy. And I think tissue is going to be the issue. And in addition to thinking about personalizing the therapy, ask what is right for this patient? Stop thinking about differentiated thyroid cancer as one big disease. This is not just—even by histology—Hürthle cell, follicular papillary, this is going to be molecularly based and very individualized—and at different time points within the same patient. And doing more research in terms of patient reported outcomes.

We certainly looked at medullary thyroid cancer, which is different, but the patients who are about to be started on cabozantinib looked like stage IV lung cancer patients, and we keep calling these patients, by physician-reported outcomes, as asymptomatic. So, just thinking about that. And then don’t forget about local therapy. Even if the patient you think needs systemic therapy, maybe they might need a bone metastasis radiated, or a metastasectomy, or something done for local things. So, don’t forget about that. Or hold the drug, do some neck surgery because of central disease, and put them back on the drug.

The last thing I want to say is, let’s not tell our patients that if you have to have a cancer, this is the best cancer to have. Not a week goes by without a patient telling me they were told that. It’s very sad.

R. Michael Tuttle, MD: Frank?

Frank Worden, MD: Going back to what the panel has said here, I think we can’t underestimate quality of life. We’re looking for targets, we’re looking for treatments and sequencing, which is all important. But, at the same time, we need to take into consideration that none of us are taking these drugs; we’re prescribing them. And it’s important that we develop these relationships with patients and their families to ensure that we can make this into a chronic disease and that the quality of life is really important.

In the DECISION study, there was very nice quality-of-life data that show that it does drop off, but it can be maintained, and I think we need to find mechanisms to do that. And we need more studies in that realm, as well. I agree with the personalized reporting. There’s data from a head and neck cancer study where patients report their data as compared to what physicians perceived the data, and there is an interesting difference you can see in that side-effect profile. And I think for the Centers of Disease Excellence, I know in head and neck cancer patients, as well, there’s now published data saying that patients who were seen at Centers of Excellence or large academic centers do better than patients who are seen in the community by an oncologist or perhaps an endocrinologist who doesn’t see as many patients as we see. So, I think emphasizing that to our medical colleagues is very important.

R. Michael Tuttle, MD: Thank you very much. This has been very helpful. We’ve covered the whole range, from diagnosis through RAI refractory, and I think we really sort of touched on a lot of the difficult issues that we deal with in clinic, that it’s really hard to implement some of these guidelines. But we’re clearly moving in the right direction. On behalf of our panel, we thank you for joining us, and we hope you found this OncLive Peer Exchange informative and useful toward future practice.

Transcript Edited for Clarity