2016年8月10日最近一项II期临床研究表明，Vemurafenib (Zelboraf) 治疗对放射碘治疗无效的具有BRAF V600E突变，且之前没有接受过VEGFR多激酶抑制剂的复发的或者转移的乳头状甲状腺癌的治疗反应率达到38.5%。如果之前接受过其他多激酶抑制剂治疗，则反应率只有28.3%。

Vemurafenib Active in BRAF V600E–Positive Papillary Thyroid Cancer Refractory to Radioactive Iodine

Key Points

Vemurafenib produced a partial response in 38.5% of patients with BRAF V600E–positive recurrent or metastatic papillary thyroid cancer refractory to radioactive iodine who had never received VEGFR multikinase inhibitor treatment. 
Partial response was achieved in 28.3% of those with prior VEGFR multikinase inhibitor treatment.

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.”