Kinase Inhibitor Favorable for Drug-Resistant Thyroid Cancer

Cabozantinib (Cabometyx) treatment resulted in tumor shrinkage among patients with refractory thyroid cancer.

Findings from a clinical trial presented at the 2018 Multidisciplinary Head and Neck Cancers Symposium suggest that cabozantinib may be an effective treatment for patients with metastatic, radioactive iodine-resistant thyroid cancer.

The clinical trial showed that treatment with the kinase inhibitor shrunk tumors in 34 out of 35 patients. Notably, more than half of the patients experienced tumor shrinkage of more than 30%, according to the study.

A majority of differentiated thyroid cancers are treated with radioactive iodine (RAI) therapy, which aggregates in the tumor cells. Although the treatment can be curative and has little effect on the rest of the body, approximately 15% of patients develop drug-resistant disease, according to the study authors.

There are 2 approved kinase inhibitors indicated to treat refractory thyroid cancer; however, the therapies are not durable, the authors noted.

“Our trial shows that cabozantinib is an active agent for patients with RAI-refractory thyroid cancer and may be able to significantly improve the care of patients who are at this advanced stage of their disease,” said the lead author Marcia S. Brose, MD PhD.

In the phase 2 trial, 35 patients with metastatic, radioactive iodine-resistant thyroid cancer were treated with cabozantinib.

Of these patients, 34% experienced thyroid tumor shrinkage and 54% achieved a partial response, according to the study.

The researchers reported that 16 patients are still enrolled in the trial and the median time enrolled was 35 weeks.

Approximately 66% of patients required dose interruptions and adjustments during the trial due to adverse events, according to the study.

The most common adverse events associated with cabozantinib therapy included hyperglyemica, which was experienced by 80% of patients, followed by diarrhea, which was experienced by 77% of patients. Other toxicities included fatigue and weight loss.

Another 14% of patients experienced grade 3 to 5 events, including hypertension, increased lipase, weight loss, pulmonary embolism, and hyponatremia, according to the study.

Based on these encouraging findings, the authors said that they plan to conduct a larger, multi-center clinical trial to further evaluate the potential of cabozantinib as a treatment for RAI-resistant thyroid cancer.

Cabozantinib is currently approved to treat metastatic medullary thyroid cancer under the name Cometriq and renal cell carcinoma under the name Cabometyx.

“These results indicate cabozantinib may offer an additional treatment option to these patients that will shrink tumors and provide an additional progression-free period for our patients,” Dr Brose said.