Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial

Abstract

Abstract Background Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression-free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2. We aim to assess apatinib in patients with advanced high-grade osteosarcoma progressing upon chemotherapy. Materials and Methods This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (≥16 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months. Results A total of 37 participants were finally included into the analysis. Until final follow-up, the objective response rate (complete response + partial response) was 43.24% (16/37). The 4-month PFS rate was 56.76% (95% confidence interval [CI], 39.43%–70.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47–6.27) and 9.87 (95% CI 7.97–18.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3–4 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar-plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment-related deaths. Conclusion Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs.