Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Republic of Korea.
Endocr J. 2019 Jul 28;66(7):597-604. doi: 10.1507/endocrj.EJ18-0488. Epub 2019 Apr 19.
Sorafenib has emerged as an effective therapeutic option for radioactive iodine (RAI)-refractory, locally advanced or metastatic differentiated thyroid cancer (DTC). We investigated the efficacy and safety of sorafenib treatment in a real-world setting and unveil predictive markers of responsiveness to sorafenib. The treatment response, progression-free survival (PFS), overall survival, and adverse events (AEs) of sorafenib-treated RAI-refractory, locally advanced or metastatic DTC patients at three institutes were retrospectively reviewed, and their tumor doubling time was calculated by three investigators. Total eighty-five patients were treated with sorafenib, and seven patients discontinued sorafenib due to AEs before the first tumor assessment. The median PFS was 14.4 months, and the objective response rate was 10.3% in 78 patients who were able to evaluate the tumor response. Age, sex, histologic type, tumor location, RAI avidity, or the presence of FDG-PET uptake did not affect PFS. However, smaller tumor size (≤1.5 cm) of the target lesions in lung showed better PFS (hazard ratio [HR] 0.39, p = 0.01), and tumors with the shortest doubling time (≤6 months) had worse outcome (HR 2.70, p < 0.01). Because of AEs, dose reductions or drug interruptions were required in 64% of patients, and eventually, 23% of patients discontinued sorafenib permanently. The most common AE was hand-foot skin reaction (HFSR). Patients with severe HFSR showed better PFS, but there were no statistical significance (HR 0.65, p = 0.05). In conclusion, small tumor size and long doubling time of each target lesion can be a prognostic marker to predict the responsiveness to sorafenib in RAI-refractory DTC patients.
索拉非尼已成为放射性碘（RAI）难治性、局部晚期或转移性分化型甲状腺癌（DTC）的有效治疗选择。我们在真实环境中研究了索拉非尼治疗的疗效和安全性，并揭示了对索拉非尼反应的预测标志物。回顾了三个研究所的 RAI 难治性、局部晚期或转移性 DTC 患者接受索拉非尼治疗的治疗反应、无进展生存期（PFS）、总生存期和不良事件（AE），并由三位研究者计算了肿瘤倍增时间。共有 85 例患者接受了索拉非尼治疗，有 7 例患者因 AE 在首次肿瘤评估前停用了索拉非尼。在能够评估肿瘤反应的 78 例患者中，中位 PFS 为 14.4 个月，客观缓解率为 10.3%。年龄、性别、组织学类型、肿瘤位置、RAI 摄取率或 FDG-PET 摄取的存在均不影响 PFS。然而，肺部目标病变的肿瘤大小（≤1.5cm）越小，PFS 越好（风险比[HR]0.39，p=0.01），倍增时间最短（≤6 个月）的肿瘤预后越差（HR 2.70，p<0.01）。由于 AE，64%的患者需要减少剂量或中断药物治疗，最终有 23%的患者永久停用了索拉非尼。最常见的 AE 是手足皮肤反应（HFSR）。严重 HFSR 的患者 PFS 更好，但无统计学意义（HR 0.65，p=0.05）。总之，每个目标病变的肿瘤大小小和倍增时间长可作为预测 RAI 难治性 DTC 患者对索拉非尼反应的预后标志物。
