Approaching Treatment of Low-Volume DTC

Lori J. Wirth, MD: I want to touch on BRAF mutations briefly, because BRAF is the gene that’s most commonly mutated in thyroid cancer, primarily in papillary thyroid cancer [PTC]. We can see it in the more undifferentiated and dedifferentiated thyroid cancers as well. We know that there was the basket trial with dabrafenib and trametinib in BRAF-mutant anaplastic thyroid cancers. That showed a really good response rate, and many of those responses were durable. Dabrafenib and trametinib were FDA approved in anaplastic thyroid cancer that has BRAF mutations.

There are many patients with iodine-refractory PTC that harbors a BRAF mutation. A lot of patients who have relatively low-volume disease that is growing slowly over time are in this group. Those are patients in whom I’m sometimes reluctant to start lenvatinib. There was a phase 2 trial that OSU [The Ohio State University Comprehensive Cancer Center] participated in, and MGH [Massachusetts General Hospital] as well. It was looking at dabrafenib plus or minus trametinib in BRAF-mutant DTC [differentiated thyroid cancer]. It was a small phase 2 trial. There’s activity there for sure but not an FDA approval.

In the patients who have low-volume disease, what do you think about if you’re thinking that they’re not ready for prime-time lenvatinib?

Jennifer Sipos, MD: We’ve started looking at potentially using some of these agents, particularly dabrafenib and trametinib, for redifferentiation therapy. We’re considering using the drug for a finite period of time. In our institution [OSU], we’re using it for a month, and then giving a dose of radioactive iodine if there’s activity on the diagnostic whole-body scan. That’s a nice bridge for some of our patients with lower-volume, slowly progressive disease. We’re in the early phases of collecting the information that is working. 

But it can be challenging in some of those folks to get them to tolerate the combination of therapies. I have less experience in using that combination outside the clinical trial. But it is something we’re excited to potentially explore down the road in redifferentiation therapy. We know that some of these gene-specific targeted treatments can impact the gene expression of some of the sodium iodine metabolism and potentially increase the iodine avidity in those tumors. It’s an exciting potential bridge between the iodine and long-term systemic therapy.

Lori J. Wirth, MD: I agree. I wish we had a clinical trial that proves that there is clinical benefit, but we’re taking that approach on an off-label, case-by-case basis in patients. There is a patient population that is not going to benefit from further radioactive iodine. We know that they have cancer, but they just do not have cancer that’s bad enough to justify lenvatinib or sorafenib at the present time. We’d like to be able to help them out. Doing a short course of drug therapy, like dabrafenib plus or minus trametinib, does cause some adverse effects and toxicity. But generally, you can get people through the treatment for a month prior to radioactive iodine. Then you bring in radioactive iodine, and you’re done with treatment. You’re not committing patients to taking a cancer drug every day, week after week, for the foreseeable future. You have a month or month and a half of intensive treatment, and then they’re done. It certainly is an appealing proposition.

That’s 1 of the things I really enjoy working with our endocrinology colleagues on, because we work together as a tag team with the dabrafenib and trametinib therapy and the radioactive iodine. I always enjoy the social aspects of the multidisciplinary approach to cancers.

Jennifer Sipos, MD: Yes, it definitely makes me feel like I’m much more involved in the process. I am involved in all of the patient’s care once they get on a systemic therapy, but I feel like I’m much more involved in that process and the decision to even take that approach. It’s fun for me. I feel like I’m dipping my toe in the oncology waters, and that’s nice.

Transcript edited for clarity.