Tang Lina, Niu Xiaohui, Wang Zhen, Cai Qiqing, Tu Chongqi, Fan Zhengfu, Yao Yang
Shanghai 6th People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Beijing Jishuitan Hospital, Peking University, Beijing, China.
Front Oncol. 2022 May 26;12:811687. doi: 10.3389/fonc.2022.811687. eCollection 2022.
Anlotinib, a novel multitarget kinase inhibitor of VEGFR, FGFR, PDGFR and c-Kit, has proven to be effective and safe for refractory soft tissue sarcoma patients, but has not been examined in recurrent or metastatic primary malignant bone tumors in a clinical trial setting.
This is a multicenter single-arm trial. Patients with pathologically proven recurrent or metastatic primary malignant bone tumors were eligible. Anlotinib was administered orally at 12 mg per day. Each cycle consisted of 2 weeks of treatment followed by 1-week off-treatment. The primary endpoint was progression-free survival (PFS), as assessed in the intention-to-treat (ITT) population. Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Adverse events (AEs) were assessed per NCI CTCAE version 4.03.
A total of 42 patients were enrolled. Median PFS was 5.3 months (95% CI 3.5-8.4 months) in the overall analysis, 4.8 months (95%CI 3.5-7.1 months) in osteosarcoma patients and 2.8 months [95%CI 1.3 months to not reached (NR)] in chondrosarcoma patients. The median OS was 11.4 months (95% CI 10.1 months to NR) in the overall analysis, not reached (95% CI, NR, NR) in osteosarcoma patients and 11.4 months (95% CI 1.8 to 21.1 months) in chondrosarcoma patients. The ORR was 9.52% and DCR was 78.57%. Grade 3 or above AEs occurred in 54.76% of the patients, and included hypertension (19.05%), hypertriglyceridemia (9.52%) and pustulosis palmaris et plantaris (7.14%). No treatment-related death was reported.
Anlotinib demonstrated promising antitumor activities in recurrent or metastatic primary malignant bone tumors with manageable AEs.
安罗替尼是一种新型的VEGFR、FGFR、PDGFR和c-Kit多靶点激酶抑制剂，已被证明对难治性软组织肉瘤患者有效且安全，但尚未在复发性或转移性原发性恶性骨肿瘤的临床试验中进行研究。
这是一项多中心单臂试验。病理证实为复发性或转移性原发性恶性骨肿瘤的患者符合条件。安罗替尼口服给药，每日12mg。每个周期包括2周治疗期，随后是1周的停药期。主要终点是意向性治疗（ITT）人群中评估的无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、疾病控制率（DCR）和总生存期（OS）。根据美国国立癌症研究所（NCI）CTCAE 4.03版评估不良事件（AE）。
共纳入42例患者。总体分析中，中位PFS为5.3个月（95%CI 3.5-8.4个月），骨肉瘤患者为4.8个月（95%CI 3.5-7.1个月），软骨肉瘤患者为2.8个月[95%CI 1.3个月至未达到（NR）]。总体分析中，中位OS为11.4个月（95%CI 10.1个月至NR），骨肉瘤患者未达到（95%CI，NR，NR），软骨肉瘤患者为11.4个月（95%CI 1.8至21.1个月）。ORR为9.52%，DCR为78.57%。54.76%的患者发生3级或以上AE，包括高血压（19.05%）、高甘油三酯血症（9.52%）和掌跖脓疱病（7.14%）。未报告与治疗相关的死亡。
安罗替尼在复发性或转移性原发性恶性骨肿瘤中显示出有前景的抗肿瘤活性，且不良事件可控。
