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‘Stay tuned:’ Neoadjuvant therapy in thyroid cancer still needs research
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CHICAGO — There are many targeted agents being tested in the neoadjuvant setting for thyroid cancer, however, it is important to understand the appropriate setting for use in this population of patients, according to a speaker at the Annual Meeting of the American Thyroid Association.
“There have been many agents studied for thyroid cancer, some of which have been approved. However, many agents are potent VEGFR inhibitors and the biggest problem with these agents in the neoadjuvant setting is that patients do not heal their surgical wounds very easily when treated with VEGFR inhibitors,” Maria E. Cabanillas, MD, FACE, an oncologic endocrinologist in the department of endocrine neoplasia and hormonal disorders at The University of Texas MD Anderson Cancer Center in Houston, said during a presentation.
Cabanillas said ideal agents are the BRAF inhibitors, which do not have VEGFR activity, and the MEK inhibitors that are used in combination with BRAF inhibitors that also have minimal VEGFR activity.
Additionally, select RET inhibitors have shown promise in patients with medullary thyroid cancer who have RET mutations and in those with RET-fusion papillary, poorly differentiated and anaplastic thyroid cancer.
“These agents are not yet approved, and we know very little about the VEGFR activity of these RET inhibitors,” she said. “We also have select NTRK fusion inhibitors that are infused for patients with solid tumors with NTRK fusions, including papillary, poorly differentiated and anaplastic thyroid cancer. These inhibitors have no VEGFR activity, making them ideal in this setting.”
A significant challenge with targeted neoadjuvant therapy, however, is resistance.
“Eventually, all of these patients will develop resistance and they will succumb to their disease, but there is a difference in how quickly patients develop resistance,” Cabanillas said.
For example, patients with anaplastic thyroid cancer may develop resistance at a median of 3 months to 9 months whereas patients with differentiated thyroid cancer may develop resistance between 11 months to 18 months.
“This is why we like to take these tumors out as soon as we can, when we can,” she said.
Still, the high response rates seen with targeted neoadjuvant therapy in various clinical trials of patients with thyroid cancer appear promising, particularly for those with anaplastic thyroid cancer.
“Some of the most exciting data that we have seen come out has been with dabrafenib (Taflinar, Novartis) plus the MEK inhibitor trametinib (Mekinist, Novartis) in patients with BRAF V600E-mutant anaplastic thyroid cancer,” Cabanillas said. “These patients have responded very nicely with this combination therapy, which has turned an unresectable tumor into a resectable tumor. We have even been able to avoid placing a tracheotomy in these patients because the response is so rapid.”
Cabanillas and colleagues completed enrollment in October for an ongoing clinical trial examining three different atezolizumab (Tecentriq, Genentech) combinations with chemotherapy in patients with anaplastic and poorly differentiated thyroid cancer.
“We also have a prospective trial that will be starting soon including dabrafenib, trametinib and pembrolizumab,” she said. “In addition, although we do not know much about neoadjuvant therapy in patients with medullary thyroid cancer, we would like to explore this. We have one patient that we have treated and we have successfully resected. We will be opening a prospective trial to assess this further in 2020. Stay tuned.” – by Jennifer Southall
Reference:
Cabanillas ME, et al. Clinical Symposium: Thyroid cancer. Presented at: Annual Meeting of the American Thyroid Association; Oct. 30-Nov. 3, 2019; Chicago.
Disclosures: Cabanillas reports grant funding from Eisai, Exelixis, Genentech and Kura; and serving on the advisory boards for Blueprint, Ignyta and LOXO.