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Immunotherapy: The Future of Treatment for ATC?

Brielle Urciuoli
Published Online: Nov 08,2016

Ramona Dadu, MD

With anaplastic thyroid cancer (ATC) being a rare disease that often has poor prognoses, researchers are seeking therapies for these patients that are more promising than surgery or radiation. Some, such as Ramona Dadu, MD, are looking toward immunotherapy. But first, more information needs to be known about which patients are likely to benefit from immunotherapy, and if it should be given as a single agent or in combination with another treatment.

Dadu, assistant professor in the Department of Endocrine Neoplasia and Hormone Disorders at The University of Texas MD Anderson Cancer Center, discussed some of these points at the 2016 American Thyroid Association annual meeting. Targeted Therapies in Oncology (TTO) sat down with Dadu to learn more about what she predicts for the future of ATC treatment.

TTO:  Why do you believe that anaplastic thyroid cancer is a “hot immunogenic environment?”

Dadu: As you know, cancer immunotherapy has been one of the most exciting areas of new discoveries for patients with cancer. But not all patients respond to immunotherapy. Those who do respond, however, have a long survival time. The interaction between the immune system and the cancer cells is actually very complex. We really need to do a comprehensive evaluation of these tumors in order to classify them as immunogenic, or hot, tumor environments versus a cold, or non-immunogenic, tumor micro-environment. A hot, immunogenic environment is where there is a lot of tumor infiltration into lymphocytes within the tumor microenvironment, but the tumor cells themselves also express high levels of PD-L1, making this environment even more exhausted.

TTO:  How do you determine which patients respond to immunotherapy, and which patients do not?

Dadu: I don’t think that, to date, we have a good predictive marker of who is going to respond or including immunotherapy, for these patients. Hopefully by next year, we’ll have something coming with combination therapy, but our goal is to take the data that we presented [at the American Thyroid Association annual meeting] and transition that to a rationally-designed clinical trial where patients with ATC may benefit from this approach.

TTO:  What is the current treatment for ATC, and what will it look like in 5 or 10 years?

Dadu: For ATC, there are approved treatments, but they are treatments that don’t necessarily work so well. Therefore, we’ve been using clinical trials as our first-line therapy for metastatic anaplastic thyroid cancer. Right now, we’re hoping that targeted therapy will be the next approach to treatment for anaplastic thyroid cancer, but also the combination of targeted therapy with immunotherapy may be what’s going to provide prolonged response rates and overall survival (OS) time.

We have used targeted therapy for metastatic anaplastic thyroid cancer; we’re actually presenting a poster today on our results with the dabrafenib (Ta nlar), trametinib (Mekinist) combination or lenvatinib (Kisplyx) as a systemic therapy, for these patients. We’ve seen responses using this approach, but unfortunately, the progression-free survival (PFS) remains quite short. We are hoping that by adding immunotherapy to targeted therapy, PFS and OS may be improved.

TTO:  Are there any specific clinical trials that you’re excited about?

Dadu: I’m very excited about the way thyroid cancer eld is moving forward. For anaplastic thyroid cancer, we do have a clinical trial that will be open soon using the FDA-approved drug, lenvatinib, in combination with pembrolizumab (Keytruda), which is an immunotherapy. Hopefully it’s going to be open in the next 6 months or so.

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Immunotherapy: The Future of Treatment for ATC?
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