Low-intermediate dose of lenvatinib in anaplastic thyroid cancer is highly effective and safe

Abstract

We report two cases of anaplastic thyroid cancer (ATC) which had a very good response to a treatment with lenvatinib at 14 mg. A 73-year-old man with ATC stage IVB was operated on, undergoing a near-total thyroidectomy, and the pathological remnant tissue showed a quick and partial response to treatment with the drug. The patient had a single metastasis in the brain after 9 months, but then died due to bronchopneumonia after undergoing a neurosurgical intervention for the complete removal of the lesion. A 74-year-old woman with ATC stage IV was operated on, undergoing a near-total thyroidectomy after a neoadjuvant treatment with the drug, that was continued after surgical treatment. She had a partial remission of the local disease and of distant metastasis, which lasted for 14 months. She then died 4 months later due to cancer progression. Lenvatinib at 14 mg appears to be effective, fast and well tolerated.

Entrectinib in the neoadjuvant setting of anaplastic thyroid cancer: a case report

“…Barbaro et al described two cases of ATC with a rapid response to lenvatinib even at a low dose (14 mg). In one of the cases, lenvatinib was used in the neoadjuvant setting ( 9 ). In our patient, lenvatinib was used transiently while awaiting for the results of molecular analysis, with a rapid initial response and disease stability for some weeks.…”

“…Discussion: ATC is one of the most lethal carcinomas and is generally refractory to standard therapies. 10 The knowledge of the genomic landscape of ATC has become extremely important since it allows the use of new drugs targeting specific molecular alterations. 1 Among the actionable mutations that occur in ATC, the most common is BRAF p.V600E (50-70%).…”

“…Barbaro et al described two cases of ATC with a rapid response to lenvatinib even at a low dose (14 mg). In one of the cases, lenvatinib was used in the neoadjuvant setting 10 .…”

Neoadjuvant treatment with lenvatinib and pembrolizumab in a BRAF V600E-mutated anaplastic thyroid cancer: a case report

“…While awaiting the results of the molecular profile analysis performed on the smear and considering the fast evolution of the disease, treatment with L and P was started. Based on our previous experience ( 11 ), L was started at a lower dose, i.e., 14 mg instead of 24 mg, and P was started at the standard regimen (200 mg every 3 weeks). After 1 month (specifically 32 days after starting L and 10 days after the second infusion of P), clear clinical benefits were observed: a slight visual reduction and, most importantly, a change in the consistency of the mass, which now appeared soft and mobile.…”

Advances in targeted therapy for anaplastic thyroid carcinoma

“…期 ATC 患者疗效有限。Ito 等 [9] 在日本进行了一项Ⅱ期临床试验，入组 10 例 ATC 患者，中位无进展存活期 为 2.8 个月，结果显示，索拉非尼可能对 ATC 无效。 研究表明，ATC 异种移植模型中放疗、紫杉醇联合索拉非尼协同作用可降低 ATC 细胞活性，并显著引 起细胞凋亡，降低 ATC 的抗凋亡因子表达，减小肿瘤体积，延长小鼠的存活期 [10] 。Yun 等 [11] 对 HNHA、 索拉非尼联合放疗治疗 ATC 的协同作用进行了研究，结果显示，HNHA 和索拉非尼联合放射治疗可使半胱 氨酸蛋白酶裂解及细胞周期阻滞，从而抑制 ATC 生长。此外，HNHA 联合索拉非尼放射治疗对 ATC 的疗 效优于 HNHA 或索拉非尼放射治疗。因此，HNHA 和索拉非尼联合放射治疗可能成为治疗 ATC 的一种新 方法。 [12] 。Takahashi 等 [13] 进行一项乐伐替尼治疗晚期甲状腺癌患者的有效性及安全性的Ⅱ 期临床试验。研究结果表明，ATC 患者的中位无进展存活期为 7.4 个月，中位总存活期为 10.6 个月，在一 定程度上延长了患者的存活期。Kim 等 [14] [15] 报道了 1 例 74 岁Ⅳ期 ATC 患者，行新辅助治疗后进 行全甲状腺切除术，术后予乐伐替尼 14 mg/d，局部及远处转移病灶部分缓解甚至几乎完全缓解，并且持 续了 14 个月，后因肿瘤进展恶化而死亡。 综上所述，乐伐替尼对 ATC 患者具有一定疗效，有望成为治疗 ATC 的候选药物，但目前病例数仍较 少，须进一步扩大样本量，获得更多临床证据证实其确切疗效。 1.3 安罗替尼 安罗替尼是一种新型多激酶抑制剂，通过抑制 VEGFR、PDGFR、RET、c-Kit 和 FGFR 等激酶来抑制 肿瘤细胞增殖和血管生成。Ruan 等 [16] 研究发现，安罗替尼对 6 种 ATC 及甲状腺乳头状癌细胞均有一定抑 制作用，且动物实验显示安罗替尼可显著抑制小鼠体内移植瘤生长。Gui 等 [17] 报道了一例 67 岁 ATC 患者 术后复发后接受信迪力单抗和安罗替尼联合治疗后肿瘤明显缩小，持续缓解期达 18.3 个月。以上研究表明， 安罗替尼单药或联合治疗可为晚期 ATC 患者提供一种可行的新治疗方式。 1.4 伊马替尼 伊马替尼是一种 BCR-ABL 激酶、c-Kit 受体及 PDGFR 抑制剂，目前主要应用于慢性髓细胞性白血病 及胃肠道间质肿瘤的临床治疗。Ha 等 [18] 进行了一项伊马替尼治疗晚期 ATC 患者的Ⅱ期临床试验，纳入 8 例晚期 ATC 患者，患者部分缓解率为 25%，疾病稳定率为 50%，但完全缓解率为 0%，疗效与细胞毒性化 疗方案相当。因此，单独应用伊马替尼治疗 ATC 的有效性仍需进一步研究。但有研究发现，伊马替尼联合 其他化疗药物可提高肿瘤细胞对抗癌药物的敏感性 [19][20] 。Kim 等 [21]…”