Iwasaki Hiroyuki, Toda Soji, Murayama Daisuke, Kato Shin, Matsui Ai
Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan.
Mol Clin Oncol. 2021 Feb;14(2):28. doi: 10.3892/mco.2020.2190. Epub 2020 Dec 16.
Tyrosine kinase inhibitors (TKIs) were first approved for treating radioactive iodine-refractory differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC) 5 years ago. Among them, lenvatinib has a high response rate and has become the first-line drug for treating thyroid cancer. Although it has a high response rate, it is also characterized by a high frequency of adverse events (AEs). AEs previously reported in a phase II study occurred after the practical application of TKI therapy. However, the type and frequency of AEs that occurred were significantly different. The present study investigated the type and frequency of AEs in the real-world setting and examined their relationship with prognosis. Between June 2015 and May 2020, 111 patients (79 patients with DTC and 32 patients with ATC) were treated with lenvatinib. An investigation of lenvatinib AEs, including fatal events, revealed that fistula formation or severe tumor regrowth after the discontinuation of treatment was an AE associated with poor prognosis. In total, 11 patients with ATC (34.4%) and 7 patients with DTC (8.9%) developed skin fistula. The mortality rate among these patients was 38.9% (7/18), including three deaths caused by major bleeding and four deaths attributable to mediastinitis or pneumonia. In the DTC group, irreversible regrowth occurred in all 7 patients who required drug withdrawal because of AEs, and all patients died. Conversely, overall survival was longer among patients with DTC and hand-foot syndrome (HFS). Therefore, the present study illustrated that although lenvatinib therapy can result in severe AEs requiring dose reduction or treatment discontinuation, the HFS appearance portends a good prognosis in patients treated with lenvatinib.
酪氨酸激酶抑制剂（TKIs）于5年前首次获批用于治疗放射性碘难治性分化型甲状腺癌（DTC）和未分化甲状腺癌（ATC）。其中，乐伐替尼具有较高的缓解率，已成为治疗甲状腺癌的一线药物。尽管其缓解率较高，但也具有不良事件（AE）发生率高的特点。先前在一项II期研究中报告的AE发生在TKI治疗实际应用之后。然而，所发生的AE的类型和频率有显著差异。本研究调查了现实环境中AE的类型和频率，并研究了它们与预后的关系。在2015年6月至2020年5月期间，111例患者（79例DTC患者和32例ATC患者）接受了乐伐替尼治疗。对包括致命事件在内的乐伐替尼AE的调查显示，治疗中断后瘘管形成或严重肿瘤复发是一种与预后不良相关的AE。总共有11例ATC患者（34.4%）和7例DTC患者（8.9%）发生了皮肤瘘。这些患者的死亡率为38.9%（7/18），包括3例因大出血死亡和4例因纵隔炎或肺炎死亡。在DTC组中，所有7例因AE需要停药的患者均出现了不可逆的肿瘤复发，且所有患者均死亡。相反，DTC合并手足综合征（HFS）的患者总生存期更长。因此，本研究表明，尽管乐伐替尼治疗可能导致严重AE需要减量或停药，但HFS的出现预示着接受乐伐替尼治疗的患者预后良好。
