Vemurafenib Shows Anti Tumor Activity in Thyroid Cancer

Vemurafenib is a multi-targeted kinase inhibitor originally approved to treat melanoma patients with a BRAF mutation.

In a phase 2 clinical study, one-third of metastatic thyroid cancer participants with a BRAF mutation (BRAFV600E) treated with vemurafenib demonstrated anti-tumor activity.

Vemurafenib is a multi-targeted kinase inhibitor (MKI) originally approved to treat melanoma patients with a BRAF mutation. For the study, 51 patients with progressive radioactive iodine-refractory (RAI) papillary thyroid cancer plus a BRAF mutation were enrolled between January 2011 and January 2013.

Participants were broken into 2 cohorts: the first had 26 patients who were not previously treated with MKIs, and a second cohort with 25 patients who were treated with MKIs. Additionally, there were some individuals in both groups previously treated with chemotherapy, as well.

In cohort one, 10 patients had a partial response to vemurafenib, while an additional 9 patients achieved stable disease for at least 6 months. The combined disease control rate was 73%, and median progression free survival was 18.2 months.

In the second cohort, the participants were heavily pretreated, and 6 of the participants had a partial response, while 6 achieved stable disease for at least 6 months. The combined disease control rate for cohort 2 was 54.5%, median progression free survival was 8.9 months, and median overall survival of 14.4 months.

Overall, the side effects reported were consistent with melanoma patients; however, there were higher rates of weight loss, anemia, dysgeusia, hepatic laboratory abnormalities, and increased creatine levels.

“Due to our prior successes in treating these patients with sorafenib and lenvatinib, patients are doing better, but they still ultimately progress, and we need additional agents with different mechanisms of action,” said researcher Marcia Brose, MD, PhD. “Vemurafenib is the first non-VEGFR inhibitor to show activity in this patient population and as such is an important addition to our treatment options for these patients.”

Although vemurafenib was found effective in patients with this particular form of disease, the positive responses are only temporary, and more treatment options are needed, according to the study.

“For this group of patients, who have little to no options, that’s a significant improvement,” Brose said. “This promising clinical trial is the next step in a series of trials to identify new drugs that are fundamentally shifting the horizon, improving the outcome for patients with advanced differentiated thyroid cancer.”

The results of study were published in Lancet Oncology.