Cabozantinib shows promise as first line treatment for differentiated thyroid cancer

A kinase inhibitor called cabozantinib could be a viable therapy option for patients with metastatic, radioactive iodine-resistant thyroid cancer.

In a trial initiated and led by the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania, tumours shrunk in 34 out of 35 patients who took the drug, and more than half of those patients saw the tumour size decrease by more than 30 percent.

As part of a phase II trial, Dr Marcia S. Brose, an Associate Professor of Otorhinolaryngology: Head and Neck Surgery and director of the Center for Rare Cancers and Personalized Therapy at Penn and her team gave the drug as a first line therapy to 35 patients with metastatic, radioactive iodine-resistant thyroid cancer starting in March of 2014. Thirty-four experienced tumour shrinkage and 19 of the 35 (54 percent) achieved a partial response – defined as a shrinkage greater than 30 percent. The median time on the study was 35 weeks (range 3-197), and 16 patients are currently still enrolled. "These results indicate cabozantinib may offer an additional treatment option to these patients that will shrink tumours and provide an additional progression-free period for our patients," Dr Brose said.

Twenty-three of the 35 patients (66 percent) required dose interruptions and dose adjustments during the trial. The most common toxicities attributable to cabozantinib included hyperglycemia, which presented in 28 patients (80 percent). Twenty-seven patients experienced diarrhoea (77 percent), 26 had fatigue (74 percent), and 25 had weight loss (71 percent). Five patients experienced grade 3-5 hypertension (14 percent), 3 had grade 3-5 increase lipase (9 percent), 2 had grade 3-5 weight loss (6 percent), 2 had grade 3-5 pulmonary embolism (6 percent), and 2 had hyponatremia (6 percent).

Most cases of differentiated thyroid cancer are treated with radioactive iodine therapy. Since the thyroid absorbs nearly all of the iodine

in the human body, radioactive iodine given to a patient will concentrate in thyroid cancer cells, killing them with little effect on the rest of the body. The treatment can be curative, but about 15 percent of these patients have cancers that are resistant to the therapy. There are currently two approved treatments in these cases, both of which are kinase inhibitors – drugs that block enzymes that are crucial to a cancer cell’s ability to function. However, responses to these treatments are not durable. Once patients progress, they need additional therapeutic options.

"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 Dr Brose

Dr Brose says the data show the need for a larger, multi-centre study, plans for which are already underway.

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