Vemurafenib showed activity in patients with progressive BRAFV600E mutation-positive papillary thyroid cancer refractory to radioactive iodine, who had not previously received a multikinase inhibitor, according to a phase 2 study published in the journal The Lancet Oncology.1

Approximately half of patients diagnosed with papillary thyroid cancer have BRAF V600E mutations. Vemurafenib, a BRAF kinase inhibitor approved by the U.S. Food and Drug Administration for the treatment of BRAF-mutant melanoma, demonstrated clinical benefit for 3 patients with BRAFV600E mutation-positive papillary thyroid cancer in a phase 1 trial. Researchers evaluated the activity of vemurafenib in this patient population in a phase 2 study.

Fifty-one patients were enrolled with recurrent or metastatic papillary thyroid cancer refractory to radioactive iodine that tested positive for the BRAF V600E mutation. Patients who had not received a multikinase inhibitor targeting VEGFR were assigned to cohort 1 and patients who were previously treated with 1 were assigned to cohort 2; all participants received vemurafenib 960 mg orally twice daily.

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After a median follow-up of 18.8 months in cohort 1, results showed that the best overall response rate was 38.5% (95% CI, 20.2-59.4), all of which were partial responses.

Sixty-five percent of patients in cohort 1 and 68% of those in cohort 2 experienced grade 3 to 4 adverse events. The most common grade 3 to 4 adverse events were squamous cell carcinoma of the skin, lymphopenia, and increased γ-glutamyltransferase.

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Serious adverse events were reported in 62% and 68% of patients in cohorts 1 and 2, respectively.

The findings suggest that vemurafenib represents a potential new therapeutic option for this patient population. These results warrant a phase 3 trial.                 


  1. Brose MS, Cabanillas ME, Cohen EEW, et al. Vemurafenib in patients with BRAFV600E-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jul 22. doi: 10.1016/S1470-2045(16)30166-8. [Epub ahead of print]