Vemurafenib Active in BRAF V600E–Positive Papillary Thyroid Cancer Refractory to Radioactive Iodine
In a phase II study reported in The Lancet Oncology, Brose et al found that vemurafenib (Zelboraf) had antitumor activity in patients with BRAF V600E–positive recurrent or metastatic papillary thyroid cancer refractory to radioactive iodine.
Study Details
In the study, 26 patients without (cohort 1) and 25 patients with (cohort 2) prior vascular endothelial growth factor receptor (VEGFR) multikinase inhibitor treatment received vemurafenib at 960 mg twice daily. The primary endpoint was investigator-assessed best overall response in cohort 1, with response confirmed on 2 assessments ≥ 4 weeks apart.
Response Rates
Median duration of follow-up was 18.8 months in cohort 1 and 12.0 months in cohort 2. Partial response was achieved in 10 of 26 patients in cohort 1 (38.5%, 95% confidence interval [CI] = 20.2%–59.4%); stable disease was achieved in 9 patients (35%), for a disease control rate of 73%. Median duration of response was 16.5 months, and median progression-free survival was 18.2 months. In 22 evaluable patients in cohort 2, 6 of 22 patients (27.3%, 95% CI = 10.7%–50.2%) achieved partial response; 6 had stable disease, for a disease control rate of 55%. Median duration of response was 7.4 months, and median progression-free survival was 8.9 months.
Adverse Events
Grade 3 or 4 adverse events occurred in 65% of cohort 1 and 68% of cohort 2, with the most common being squamous cell carcinoma of the skin (27% and 20%), lymphopenia (8% in both), and increased γ-glutamyltransferase (4% and 12%). Two patients in cohort 2 died due to adverse events (dyspnea and multiorgan failure), but neither death was considered related to treatment. Serious adverse events occurred in 62% and 68% of patients.
The investigators concluded: “Vemurafenib showed anti-tumour activity in patients with progressive, BRAF V600E–positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. As such, this agent represents a potential new treatment option for these patients.”
The study was funded by F. Hoffmann-La Roche.
Marcia S. Brose, MD, of the Abramson Cancer Center of the University of Pennsylvania, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
