A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer

• Published in: Clinical cancer research 2021-10, Vol.27 (20), p.5502-5509
• Main Authors: Zheng, Xiangqian, Xu, Zhengang, Ji, Qinghai, Ge, Minghua, Shi, Feng, Qin, Jianwu, Wang, Feng, Chen, Guang, Zhang, Yuan, Huang, Rui, Tan, Jian, Huang, Tao, Li, Sijin, Lv, Zhongwei, Lin, Yansong, Guo, Zhuming, Kubota, Tomoki, Suzuki, Takuya, Ikezawa, Hiroki, Gao, Ming
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; China; Clinical Trials: Targeted Therapy; Double-Blind Method; Female; Humans; Iodine Radioisotopes - therapeutic use; Male; Middle Aged; Phenylurea Compounds - therapeutic use; Quinolines - therapeutic use; Radiation Tolerance; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - pathology; Thyroid Neoplasms - radiotherapy; Young Adult
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-21-0761

Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase III SELECT study; however, it has not been tested in Chinese patients with RR-DTC. Chinese patients with confirmed RR-DTC ( = 151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for progression-free survival and objective response rate were conducted using Response Evaluation Criteria in Solid Tumors v1.1 and confirmed by independent imaging review. All adverse events were assessed and monitored. Progression-free survival was significantly longer with lenvatinib treatment [ = 103; median 23.9 months; 95% confidence interval (CI), 12.9-not estimable] versus placebo ( = 48; median 3.7 months; 95% CI, 1.9-5.6; hazard ratio = 0.16; 95% CI, 0.10-0.26; < 0.0001). The objective response rate was 69.9% (95% CI, 61.0-78.8) in the lenvatinib arm and 0% (95% CI, 0-0) in the placebo arm. At data cutoff, 60.2% of patients receiving lenvatinib remained on treatment; treatment-emergent adverse events led to lenvatinib discontinuation in 8.7% of patients. Overall, treatment-emergent adverse events of grade ≥3 occurred in 87.4% of patients in the lenvatinib arm, the most common being hypertension (62.1%) and proteinuria (23.3%). Lenvatinib at a starting dose of 24 mg/day significantly improved progression-free survival and objective response rate in Chinese patients with RR-DTC versus placebo. There were no new or unexpected toxicities. Results are consistent with those from SELECT involving patients with RR-DTC.