‘Rational combination therapies’ stand as the next step in thyroid cancer
CHICAGO — Bryan R. Haugen, MD, professor of medicine in the department of medicine-endocrinology, metabolism and diabetes at the University of Colorado School of Medicine received the 2019 Sydney H. Ingbar award during the Annual Meeting of the American Thyroid Association.
The award recognizes Haugen as an established investigator who has made outstanding contributions to thyroid-related research.
He received the award for his work in thyroid cancer, including the discovery of increased telomerase activity in malignant thyroid nodules. He additionally was a part of the research group that established the use of recombinant human TSH for remnant ablation in thyroid cancer.
“More recently, Dr. Haugen is known as the lead author of the 2015 ATA guidelines on the evaluation and management of thyroid nodules in thyroid cancer,” Michael T. McDermott, MD, physician in the department of endocrinology, diabetes and metabolism at the University of Colorado Health Diabetes and Endocrinology Clinic-Anschutz Medical Campus, said during a presentation. “Other than being a great researcher, Dr. Haugen is a great clinician, wonderful teacher and a great friend.”
During his presentation, Haugen acknowledged Dr. Ingbar as a giant in thyroidology.
“It is truly a humbling honor to receive the Sydney H. Ingbar award and give this lecture,” he said.
The theme of Haugen’s talk focused on some of the ongoing research he and colleagues are working on to develop better treatment options for patients with advanced-stage thyroid cancer.
“One of the original targeted therapies in thyroid cancer, radioiodine therapy, is truly something that medical oncologists have always been jealous of us having as a targeted therapy for patients with differentiated thyroid cancer,” he said.
There have been tremendous breakthroughs in the field, according to Haugen.
“Beginning in the 1980s, the FDA approved doxorubicin for differentiated thyroid cancer. It was not until 33 years later that sorafenib (Nexavar; Bayer, Onyx Pharmaceuticals) was approved in 2013, followed by lenvatinib (Lenvima, Eisai) in 2015. We have had a flurry of approvals of agents for these advanced cancers,” Haugen said. “Then, in 2017, we had the very impressive approval of pembrolizumab (Keytruda, Merck) based upon mutational status, which included patients with thyroid cancer. Of course, 2018 brought about two additional approvals, including the combination of dabrafenib (Tafinlar, GlaxoSmithKline) plus trametinib (Mekinist, GlaxoSmithKline) in patients with BRAF-mutant anaplastic thyroid cancer and larotrectinib (Vitrakvi; Bayer, Loxo Oncology) for patients with NTRK-fusion thyroid cancer. This year, entrectinib (F. Hoffman-LaRoche) was also approved for NTRK-fusion thyroid cancer.”
Despite the tremendous progress made, Haugen said most treatments are single-agent therapies and there is a need for combination treatments.
“We need to think about and develop combination therapies for these patients. While dabrafenib plus trametinib is a combined therapy, it only targets one pathway,” he said. “This has led to the ongoing work by my colleagues and I working on rational combination therapies for patients with advanced-stage disease. Five years ago, our hypothesis was that synergistic rationally selected drug combinations with the anchor drug lenvatinib in differentiated or anaplastic thyroid cancer and taxanes in anaplastic thyroid cancer will be more effective than monotherapy and that combination therapies may delay the development of drug-resistance and could potentially improve patient survival.”
Haugen and colleagues are using three basic methods for their discovery-based approach to combination therapies.
“We are focusing on identification of synthetic lethal vulnerabilities using functional genomics, defining genomics predictors of the sensitivity to taxanes and levatinib using ‘big data’ cancer pharmacogenomics and we are using ‘brute force’ testing of multiple drug combinations with an automated in vitro synergy assay,” he said. “This is what we have been working on for the past 5 or 6 years, with the hope of moving our discovery-based work into preclinical models and hopefully into clinical trials and eventually into the clinic.” – by Jennifer Southall
Haugen BR, et al. Sidney H. Ingbar Award Lecture. Presented at: Annual Meeting of the American Thyroid Association; Oct. 30-Nov. 3, 2019; Chicago.
Disclosures: Haugen reports no relevant financial disclosures.