Safety and Effectiveness of Lenvatinib in 594 Patients with Unresectable Thyroid Cancer in an All-Case Post-Marketing Observational Study in Japan
Safety and Effectiveness of Lenvatinib in 594 Patients with Unresectable Thyroid Cancer in an All-Case Post-Marketing Observational Study in Japan
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DOI：
10.1007/s12325-020-01433-8
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发表时间：
2020-07-16
影响因子：
3.8
通讯作者：
Yoshida, Akira
中科院分区：
文献类型：
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作者：
Takahashi, Shunji;Tahara, Makoto;Yoshida, Akira
乐伐替尼在日本获批用于治疗所有组织学亚型的不可切除甲状腺癌患者，包括分化型甲状腺癌（DTC）、甲状腺髓样癌（MTC）和甲状腺间变性癌（ATC）。然而，日本患者的安全性和有效性数据有限。因此，这项前瞻性、上市后观察性研究在日常临床实践中评价了乐伐替尼在不可切除的甲状腺癌日本患者中的安全性和有效性。方法登记2015年5月至11月期间首次接受乐伐替尼治疗的所有不可切除甲状腺癌患者。患者口服乐伐替尼并随访12个月。终点包括药物不良反应（ADR）、总生存期（OS）、总缓解率（ORR）和至治疗失败时间。进行事后考克斯多变量分析，以评估与12个月OS率相关的预后因素。结果在629例登记患者中，594例纳入分析。共有442例患者（74.4%）患有DTC，28例患者（4.7%）患有MTC，124例患者（20.9%）患有ATC。在所有组织学亚型中，高血压、蛋白尿和掌跖红肿综合征是最常报告的ADR。ATC患者的中位OS为101.0天，DTC患者和MTC患者未达到，12个月OS率分别为15.6%、75.7%和83.0%。在368例DTC、20例MTC和105例ATC患者中，ORR分别为59.2%、45.0%和43.8%。多因素分析显示，东部肿瘤协作组体能状态（ECOG PS）、肿瘤大小、肿瘤浸润和体重是影响DTC患者OS的基线预后因素，而ECOG PS和肝转移是ATC患者的预后因素。结论：在日本的真实环境中，乐伐替尼在甲状腺癌患者中的安全性特征可接受。本研究中乐伐替尼的安全性特征和有效性结果与既往临床试验的结果一致，不考虑组织学亚型。
Introduction Lenvatinib is approved in Japan for treating patients with all histological subtypes of unresectable thyroid cancer, including differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC). However, safety and effectiveness data are limited in Japanese patients. Therefore, this prospective, post-marketing observational study evaluated, in daily clinical practice, the safety and effectiveness of lenvatinib in Japanese patients with unresectable thyroid cancer. Methods All patients with unresectable thyroid cancer first treated with lenvatinib between May and November 2015 were registered. Patients were orally administered lenvatinib and followed up for 12 months. The endpoints included adverse drug reactions (ADRs), overall survival (OS), overall response rate (ORR), and time-to-treatment failure. Post hoc Cox multivariate analyses were performed to assess prognostic factors associated with the 12-month OS rate. Results Of 629 registered patients, 594 were included in the analysis. A total of 442 patients (74.4%) had DTC, 28 (4.7%) had MTC, and 124 (20.9%) had ATC. Hypertension, proteinuria, and palmar-plantar erythrodysesthesia syndrome were the most frequently reported ADRs across all histological subtypes. The median OS was 101.0 days in patients with ATC which was not reached in patients with DTC and patients with MTC, with 12-month OS rates of 15.6%, 75.7%, and 83.0%, respectively. The ORRs were 59.2%, 45.0%, and 43.8% among 368 patients with DTC, 20 with MTC, and 105 with ATC, respectively. Multivariate analyses revealed that Eastern Cooperative Oncology Group performance status (ECOG PS), tumor size, the presence of tumor invasion, and body weight were baseline prognostic factors affecting OS in patients with DTC, while ECOG PS and the presence of liver metastasis were prognostic factors in patients with ATC. Conclusion Lenvatinib demonstrated an acceptable safety profile for patients with thyroid cancer in a real-world setting in Japan. The safety profile and effectiveness findings for lenvatinib in this study were consistent with those from previous clinical trials, irrespective of histological subtype.