Single-Agent TKIs Effective in Treating Thyroid Cancers That Respond Poorly to Other Treatments: Presented at WCTC

By Cameron Johnston

TORONTO -- August 10, 2009 -- Both sunitinib and sorafenib, used as single agents, appear to be useful for treating differentiated thyroid cancer that has failed to respond to radioactive iodine therapy, according to a study presented here on August 9 at the annual World Congress on Thyroid Cancer (WCTC).

According to Maria Cabanillas MD, University of Texas M. D. Anderson Cancer Center, Houston, Texas, 1 in 5 patients with differentiated thyroid cancer will develop distant metastasis, and of those, 50% will not respond well to iodine therapy.

Therefore, the advent of tyrosine kinase inhibitors (TKIs) has been a welcome addition to the list of possible treatments clinicians can offer those patients. However, she added, to date, TKIs have only been used in multiple-drug regimens. This study is believed to represent the first time they have been used as single agents to treat the disease.

The study enrolled 33 patients, but 18 were disqualified because they had received multiple drug therapies, or for other reasons. In the present analysis, 13 patients received sorafenib, and 2 received sunitinib. Both patients receiving sunitinib had tried, and failed treatment with sorafenib.

The patient's median age was 61 years and median time on therapy was a 49 weeks (range, 13-81 weeks).

The data showed that 3 out of 15 patients (20%) had a partial response to TKI therapy, 9 (60%) had stable disease, and 3 (20%) had tumours that continued to progress even after treatment. This represents a clinical benefit rate of 80%, Dr. Cabanillas said, with a durable response rate seen in 10 of the 15 (66%).

Dr. Cabanillas pointed out that the improvements seen in the patients' lungs were more robust than the responses seen in the lymph nodes. Lung metastasis showed a median regression of 16%, compared with a progression of 3% in the patients' lymph nodes.

The single-agent drugs also produced significant improvements in progression-free survival (19 for TKI compared with 4 months when they were not on TKI; P = .001). Dr. Cabanillas said the median overall survival had not yet been reached, but in these patients would be greater than 24 months.

The response to TKI therapy was similar in patients regardless of the tumour histology. Furthermore, 6 of 8 patients with papillary carcinoma underwent genetic testing for BRAF mutation and 3 of these patients were also confirmed positive for another mutation, V600E, also associated with a more aggressive disease.

Although single-agent TKIs proved beneficial in this small group of patients, Dr. Cabanillas cautioned that these patients had differentiated cancers which are easier to treat than medullary or anaplastic cancers. As a result, it is not possible to generalise these findings to patients with other sub-types of thyroid cancer.

[Presentation title: Treatment With Tyrosine Kinase Inhibitors (TKIs) for Patients With Differentiated Thyroid Cancer (DTC): The MD Anderson Cancer Center Experience. Abstract P29]