Anlotinib for Recurrent or Metastatic Primary Malignant Bone Tumor: A Multicenter, Single-Arm Trial

Lina Tang; Xiaohui Niu; Zhen Wang; Qiqing Cai; Chongqi Tu; Zhengfu Fan; Yang Yao

doi:10.3389/fonc.2022.811687

Anlotinib for Recurrent or Metastatic Primary Malignant Bone Tumor: A Multicenter, Single-Arm Trial

Front Oncol. 2022 May 26:12:811687. doi: 10.3389/fonc.2022.811687. eCollection 2022.

Authors

Lina Tang¹, Xiaohui Niu², Zhen Wang³, Qiqing Cai⁴, Chongqi Tu⁵, Zhengfu Fan⁶, Yang Yao¹

Affiliations

¹ Shanghai 6th People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
² Beijing Jishuitan Hospital, Peking University, Beijing, China.
³ Department of Orthopaedics, The First Affiliated Hospital, The Air Force Medical University, Xi'an, China.
⁴ Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China.
⁵ Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China.
⁶ Beijing Cancer Hospital, Peking University, Beijing, China.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Anlotinib demonstrated promising antitumor activities in recurrent or metastatic primary malignant bone tumors with manageable AEs.

Keywords: angiogenesis; anlotinib; chondrosarcoma; multitarget tyrosine kinase inhibitor; osteosarcoma; progress-free survival.