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

Abstract

ObjectiveAnlotinib, 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.MethodsThis 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.ResultsA 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.ConclusionAnlotinib demonstrated promising antitumor activities in recurrent or metastatic primary malignant bone tumors with manageable AEs.