Case 3: Disease Management Considerations


The panel of experts share their treatment recommendations for a 64-year-old woman with RET wild-type metastatic MTC.

Marcia Brose, MD: Let’s just pull these things together. How do the data on the vandetanib and cabozantinib trials inform your practice? Andrew, what’s noteworthy about these studies? I know these have been out longer than the studies we’ve just talked about.

Andrew Gianoukakis, MD: At the time when the drugs were approved, we had nothing for metastatic disease. In contrast with differentiated thyroid cancer, where we had radioactive iodine, for medullary [thyroid cancer], surgical therapy was the only option. It was great to have these 2 drugs approved close to each other. It’s effective in giving us an opportunity to offer our patients something when nothing existed medically. The drugs have adverse effects, but they’re both efficacious. Cabozantinib was used in a group of patients that are progressing, and there’s also clear efficacy in the 918T subgroup of patients. In a patient like this, I’d take both the progression and the 918T mutation into consideration and, between the 2, go with cabozantinib.

Marcia Brose, MD: Lori, do you want to give us your summation? You can pick any of these discussion points that you want to respond to. What’s your take on vandetanib and cabozantinib? How does it fit into your care paradigm? Especially for patients who don’t have RET mutations, because this seems to be a place where they are unique.

Lori Wirth, MD: For patients who don’t have RET mutations, it’s OK because we’ve got 2 good drugs. Both vandetanib and cabozantinib have really good activity, with adverse-effect profiles that have to be managed but that are generally manageable for most patients. I’ve been struck by several of my patients with metastatic MTC [medullary thyroid cancer], with and without RET mutations, having prolonged disease responses with vandetanib. In my hands, I have been impressed with people being able to stay on vandetanib a little easier over long periods of time compared with cabozantinib. In general, I’ve gone back and forth about which is a better drug to use first in these patients. I tend to use vandetanib more than cabozantinib, the opposite of Andrew’s approach. There’s no head-to-head comparison. It needs to be an individualized patient and a decision for each patient, and it’s hard to know what the right answer is.

Marcia Brose, MD: Andrew said that he uses cabozantinib first, but certainly for patients who have active disease with lots of tumor burdens, particularly in the liver, that might be the patient that I would collect more for cabozantinib. But like you, I’ve had patients who required dose reductions on vandetanib, sometimes to 200 or 100 mg a day, who did well for 4 or 5 years. I’m not taking them off to put them on the RET inhibitors when I find out that they have a RET mutation, because they’re doing great. We’ve got something in the bag because they were started on vandetanib before that was an option. I don’t think we necessarily need to stop them from these therapies if they’re tolerating them well.

Lori Wirth, MD: I agree. You don’t want to mess with success.

Marcia Brose, MD: Exactly. They’ll need something else later for sure. Are there any closing remarks?

Andrew Gianoukakis, MD: What’s the next step for a patient who fails? That’s an important question if we’re going to keep it there. What are the next steps for a RET wild-type patient who fails on vandetanib or cabozantinib?

Lori Wirth, MD: In the exam trial there were patients who had received prior vandetanib, and those patients can respond to cabozantinib. If the patient was treated with vandetanib and progressed, cabozantinib would be my next go-to drug. The other thing that’s worth mentioning is that lenvatinib was studied in a phase 2 trial of MTC, and also has good activity in MTC. We should have done a registrational trial with lenvatinib in these patients. I’ve used lenvatinib in these patients as well, off-label, and seen some good activity. One last thing I would say is that the second most common potentially actionable mutation in MTC involves NRAS or HRAS. We need to figure out how to drug NRAS and HRAS. There are clinical trials that these might be eligible for that are worth trying to pursue.

Marcia Brose, MD: Great. I’ll turn it back to you, Lori.

Lori Wirth, MD: I just want to close things by saying thank you so much to Dr Gianoukakis and Dr Brose for serving on the panel, for your thoughtful discussion and presentations, and this lively and informative discussion. I also want to thank the viewing audience. Thank you for joining us for this Targeted OncologyVirtual Tumor Board® presentation. We hope that today’s discussion was valuable and that you acquired some practical knowledge that you can take back to your clinic. Thanks so much for joining us.

This transcript has been edited for clarity.

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