Tahara Makoto, Kiyota Naomi, Yamazaki Tomoko, Chayahara Naoko, Nakano Kenji, Inagaki Lina, Toda Kazuhisa, Enokida Tomohiro, Minami Hironobu, Imamura Yoshinori, Sasaki Tatsuya, Suzuki Takuya, Fujino Katsuki, Dutcus Corina E, Takahashi Shunji
Department of Head and Neck Medical Oncology, National Cancer Center Hospital East , Kashiwa , Japan.
Department of Medical Oncology and Hematology, Kobe University Hospital , Kobe , Japan.
Front Oncol. 2017 Mar 1;7:25. doi: 10.3389/fonc.2017.00025. eCollection 2017.
Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need.
This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate.
At data cutoff, 17 patients with ATC were enrolled. All experienced ≥1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%.
In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC.
NCT01728623.
乐伐替尼已获日本、美国和欧盟监管机构批准，用于治疗放射性碘难治性分化型甲状腺癌（RR-DTC）。然而，甲状腺癌是一种临床异质性疾病，包括间变性甲状腺癌（ATC），这是致死率最高的亚型。ATC的有效治疗方法尚属未满足的需求。
这项2期单臂开放标签研究于2012年9月3日至2015年7月9日在甲状腺癌患者中开展，包括ATC、RR-DTC和甲状腺髓样癌患者。患者每日接受24mg乐伐替尼治疗，直至疾病进展或出现不可接受的毒性。主要终点为安全性，次要终点为疗效，通过无进展生存期（PFS）、总生存期（OS）和客观缓解率进行评估。
在数据截止时，纳入了17例ATC患者。所有患者均经历了≥1次治疗中出现的不良事件（TEAE）。最常见的TEAE为食欲减退（82%）、高血压（82%）、疲劳（59%）、恶心（59%）和蛋白尿（59%）。值得注意的是，仅1例患者因TEAE需要停用乐伐替尼，且该TEAE被认为与乐伐替尼无关。中位PFS为7.4个月[95%置信区间（CI）：1.7 - 12.9]，中位OS为10.6个月（95%CI：3.8 - 19.8），客观缓解率为24%。
在本研究中，乐伐替尼在ATC患者中显示出通过剂量调整可管理的毒性及临床活性。乐伐替尼的这种临床活性值得在ATC中进一步研究。
NCT01728623
