Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.
Department of Thoracic Oncology, Hyogo Cancer Center, Hyogo, Japan.
Lancet Oncol. 2020 Jun;21(6):843-850. doi: 10.1016/S1470-2045(20)30162-5.
Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma.
This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777.
Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events.
The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma.
Center for Clinical Trials, Japan Medical Association.
胸腺癌是一种罕见的恶性疾病，先前接受铂类化疗治疗的晚期或转移性胸腺癌的标准治疗尚未确立。仑伐替尼是一种新型的多靶点 VEGFR、FGFR、RET、c-Kit 及其他激酶抑制剂。本试验旨在评估仑伐替尼作为二线治疗在胸腺癌中的疗效和安全性。
本研究在日本的 8 家机构（5 家癌症中心、2 家医科大学附属医院和 1 家公立医院）进行，共纳入病理证实的不可切除的晚期或转移性胸腺癌患者，这些患者在至少一次铂类化疗后进展。主要纳入标准为年龄 20 岁或以上，至少有一个可测量的病灶，根据实体瘤反应评估标准 1.1 版定义，东部肿瘤协作组体能状态为 0 或 1。患者以 24mg 仑伐替尼每日口服一次，每 4 周为一个周期，直至疾病进展或出现不可接受的不良事件。主要终点为意向治疗人群中独立中心评估的客观缓解率，数据截止日期为 2019 年 2 月 22 日。本试验在 JMACCT、JMA-IIA00285 和 UMIN-CTR 上注册，注册号分别为 UMIN000026777。
2017 年 4 月 21 日至 2018 年 2 月 22 日期间，共纳入 42 例患者，所有患者均纳入疗效和安全性分析。中位随访时间为 15.5 个月（IQR 13.1-17.5）。客观缓解率为 38%（90%CI 25.6-52.0，p<0.0001）。42 例患者中 16 例（38%）有部分缓解，24 例（57%）有疾病稳定。最常见的 3 级治疗相关不良事件是高血压（27 例[64%]）和掌跖红斑感觉不良综合征（3 例[7%]）。无患者因不良事件死亡。
在晚期或转移性胸腺癌患者中，仑伐替尼的疗效和安全性得到了证实。这些结果表明，仑伐替尼可能成为先前接受治疗的晚期或转移性胸腺癌患者的标准治疗选择。
日本医学会临床研究中心。
