Genetic Analysis of Thyroid Cancer Suggests Personalized Treatment Possible

In April, researchers from the University of Colorado Cancer Center completed the largest study of thyroid cancer genetics to date, the results of which were published in Clinical Cancer Research.

The study included data from 583 patient samples of advanced differentiated and 196 anaplastic thyroid cancers (ATC) generated from targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne CDx. Researchers looked to identify genetic alterations that had potential diagnostic, prognostic, and therapeutic significance.

FoundationOne CDx is the first-of-a-kind comprehensive companion diagnostic test for solid tumors that made history in December 2017 when it was under parallel review and subsequent approval by both the FDA and CMS. The test helps to identify which patients may benefit from on-label targeted therapies. Both FoundationOne CDx and MSK-IMPACT are commonly used for cancer genotyping in clinical practice. By combining data generated from both panels, researchers were able to compile the largest collection of genetic alterations in advanced thyroid cancer to date.

In analyzing the data found from the next-generation sequencing tests, the study authors found that in several samples of advanced differentiated thyroid cancer and ATC, mechanisms to repair DNA were broken and led to a subset of thyroid cancers that had a high mutational burden.

In addition, researchers also found specific genetic mutations associated with anaplastic cancers, including amplifications of the KDR, KIT, and PDGFRA genes. These receptor tyrosine kinases enable cancer cells to reproduce more quickly, and are targeted by lenvatinib, an FDA-approved drug to treat kidney cancer. Researchers administered this drug to a cohort of participants within the study, and found that the cell line that amplified KDR, KIT, and PDGFRA responded well to the drug, suggesting that treatment with lenvatinib could show promising results.

Finally, the study also identified several genetic alterations that may be vital for the development of personalized therapies for thyroid cancer. The amplification of CD274, PDCD1LG2, JAK2, and DNA mismatch repair (MMR) deficiencies have been associated with a positive response to immune checkpoint inhibitors such as pembrolizumab and nivolumab.

“As a clinician, I learn from this study that every patient with advanced thyroid cancer that we consider for systemic therapy should be genotyped—knowledge of genetic background may affect how we treat that patient,” said the lead study author, Nikita Pozdeyev, MD, PhD, assistant professor of medicine, endocrinology, metabolism, and diabetes at the University of Colorado School of Medicine, in a statement. “There are many drugs targeting many genetic changes that are approved for other cancers, which we would not usually think to use in thyroid cancer. Some of the findings in this paper will potentially change that.”

Reference

Pozdeyev N, Gay L, Sokol E, et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers [published online May 22, 2018]. Am J Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-0373.