Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

中文翻译：

---

达拉非尼和曲美替尼治疗局部晚期或转移性 BRAF V600 突变型甲状腺未分化癌患者

目的我们报告达拉非尼（BRAF 抑制剂）和曲美替尼（MEK 抑制剂）联合治疗 BRAF V600E 突变的间变性甲状腺癌的疗效和安全性. 方法 在这项 II 期开放标签试验中，患有预先确​​定的 BRAF V600E 突变恶性肿瘤的患者接受达拉非尼 150 mg 每天两次和曲美替尼 2 mg 每天一次，直至出现不可接受的毒性、疾病进展或死亡。主要终点是研究者评估的总体反应率。次要终点包括反应持续时间、无进展生存期、总生存期和安全性。结果 16 名 BRAF V600E 突变的间变性甲状腺癌患者是可评估的（中位随访时间，47 周；范围，4 至 120 周）。所有患者都曾接受过放射治疗和/或手术，其中 6 人曾接受过全身治疗。确认的总体响应率为 69%（16 个中的 11 个；95% CI，41% 至 89%），有 7 个持续响应。由于缺乏事件，中位反应持续时间、无进展生存期和总生存期未达到，12 个月的估计值分别为 90%、79% 和 80%。安全人群由 100 名患者组成，这些患者有七种罕见的肿瘤组织学。常见的不良事件是疲劳 (38%)、发热 (37%) 和恶心 (35%)。没有检测到新的安全信号。结论 达拉非尼加曲美替尼是第一个被证明在 BRAF V600E 突变的间变性甲状腺癌中具有强大临床活性并且耐受性良好的方案。