Kim Mijin, Jin Meihua, Jeon Min Ji, Kim Eui Young, Shin Dong Yeob, Lim Dong Jun, Kim Bo Hyun, Kang Ho-Cheol, Kim Won Bae, Shong Young Kee, Kim Hee Kyung, Kim Won Gu
Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Thyroid. 2023 Jan;33(1):91-99. doi: 10.1089/thy.2022.0054. Epub 2022 May 17.
Sorafenib and lenvatinib have been widely adopted to treat radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). However, limited data exist regarding a direct comparison of these tyrosine kinase inhibitors (TKIs). We aimed to evaluate the clinical efficacy and safety of two TKIs as first-line therapy in patients with distant metastatic or locally advanced, progressive, RAI-refractory DTC in real-world practice. In this multicenter, retrospective cohort study, we evaluated 136 patients with progressive distant metastatic or locally advanced, progressive, RAI-refractory DTC or poorly differentiated thyroid carcinoma (PDTC) who received first-line sorafenib or lenvatinib treatment. The primary outcome was progression-free survival (PFS). We also evaluated the objective response rate, disease-control rate, clinical benefit rate, and safety. The median age of the patients was 68 years, and 35% (47/136) were male. Eighty and fifty-six patients were included in the sorafenib and lenvatinib groups, respectively. The median PFS was 13.3 months [95% confidence interval, CI, 9.9-18.1 months] in the sorafenib group and 35.3 months [CI, 18.2 months to upper limit not reported as the median was not reached] in the lenvatinib group ( = 0.001). A significantly prolonged PFS was observed in the lenvatinib group (compared with the sorafenib group) after adjusting for age, sex, pathology, disease-related symptom, lung-only metastasis, cumulative RAI dose, time from diagnosis, treatment duration, and longest diameter of the target lesion (hazard ratio = 0.34, CI, 0.19-0.60, < 0.001). The partial response rate was 24% and 59% in the sorafenib and lenvatinib groups, respectively ( < 0.001). More common grade 3-4 adverse events were hypertension (16%, 9/56 vs. 1%, 1/80, = 0.002) and proteinuria (32%, 18/56 vs. 0%, < 0.001) in the lenvatinib group, and hand-foot skin reaction (24%, 19/80 vs. 4%, 2/56, = 0.001) in the sorafenib group. In our study of Asian patients, first-line lenvatinib treatment of metastatic or locally advanced, progressive, RAI-refractory DTC or PDTC was associated with a longer PFS compared with sorafenib. However, severe hypertension and proteinuria were observed more frequently after lenvatinib treatment than after sorafenib treatment.
索拉非尼和乐伐替尼已被广泛用于治疗放射性碘（RAI）难治性分化型甲状腺癌（DTC）。然而，关于这些酪氨酸激酶抑制剂（TKIs）直接比较的数据有限。我们旨在评估这两种TKIs作为一线治疗远处转移或局部晚期、进展性、RAI难治性DTC患者在实际临床中的疗效和安全性。在这项多中心回顾性队列研究中，我们评估了136例接受一线索拉非尼或乐伐替尼治疗的进展性远处转移或局部晚期、进展性、RAI难治性DTC或低分化甲状腺癌（PDTC）患者。主要结局是无进展生存期（PFS）。我们还评估了客观缓解率、疾病控制率、临床获益率和安全性。患者的中位年龄为68岁，35%（47/136）为男性。索拉非尼组和乐伐替尼组分别纳入80例和56例患者。索拉非尼组的中位PFS为13.3个月[95%置信区间（CI），9.9 - 18.1个月]，乐伐替尼组为35.3个月[CI，18.2个月至上限未报告，因为未达到中位值]（P = 0.001）。在调整年龄、性别、病理、疾病相关症状、仅肺转移、累积RAI剂量、诊断时间、治疗持续时间和靶病灶最长直径后，乐伐替尼组（与索拉非尼组相比）观察到PFS显著延长（风险比 = 0.34，CI，0.19 - 0.60，P < 0.001）。索拉非尼组和乐伐替尼组的部分缓解率分别为24%和59%（P < 0.001）。乐伐替尼组更常见的3 - 4级不良事件是高血压（16%，9/56 vs. 1%，1/80，P = 0.002）和蛋白尿（32%，18/56 vs. 0%，P < 0.001），索拉非尼组是手足皮肤反应（24%，19/80 vs. 4%，2/56，P = 0.001）。在我们对亚洲患者的研究中，一线乐伐替尼治疗转移性或局部晚期、进展性、RAI难治性DTC或PDTC与索拉非尼相比，PFS更长。然而，乐伐替尼治疗后观察到的严重高血压和蛋白尿比索拉非尼治疗后更频繁。
