Immunotherapy Potentially Promising for Treatment of ATC

Ramona Dadu, MD

Given the poor prognoses often seen in patients with anaplastic thyroid cancer (ATC), researchers are seeking novel therapies that may hold more promise than surgery or radiation. Such solutions may be found with immunotherapy, though questions remain as to which patients will benefit from which drugs, and whether these therapies should be administered as single agents or in combination with other treatments.

"I don’t think that, to date, we have a good predictive marker of who is going to respond or not [to immunotherapy], and that’s why all of these areas of research we’re performing right now are meant to identify those patients or any predictive markers of worse outcomes, survival, or even selection for immunotherapy," said Ramona Dadu, MD.

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

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

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.I don’t think that, to date, we have a good predictive marker of who is going to respond or not [to immunotherapy], and that’s why all of these areas of research we’re performing right now are meant to identify those patients or any predictive markers of worse outcomes, survival, or even selection for immunotherapy.

Where are we currently with the immunoprofiling of ATC tumors, and what more needs to be done?

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

In thyroid cancer, immunotherapy is not approved for treatment, but we are hoping that by identifying all of these immune infiltrates and PD-L1 expression, we will be able to move the field forward with immunotherapy in thyroid cancer. Few patients with thyroid cancer have been treated with immunotherapy [on clinical trials], so the data is quite limited.As you know, anaplastic thyroid cancer is exceedingly rare and also rapidly fatal. There were a lot of limitations in testing and understanding tumor biology. Fortunately, at MD Anderson, we are a research center for patients with anaplastic thyroid cancer and we have a large cohort of anaplastic thyroid cancer patients. Therefore, we are able to not only start looking at tissues, but also start opening clinical trials with combination therapies, 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 bene t from this approach.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.

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

We have used targeted therapy for metastatic anaplastic thyroid cancer; we’re actually presenting a poster today on our results with the dabrafenib (Tafinlar), trametinib (Mekinist) combination or lenvatinib (Lenvima) 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.I’m very excited about the way thyroid cancer field 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.

Dadu, an assistant professor in the Department of Endocrine Neoplasia and Hormone Disorders at the University of Texas MD Anderson Cancer Center, discussed these points and more at the 2016 American Thyroid Association annual meeting. In an interview with OncLive, she sheds light on her predictions for the future of ATC treatment.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.