Clinical study of apatinib in the treatment of stage IV osteogenic sarcoma after failure of chemotherapy

Abstract

Objective: To analyze the efficacy and safety of apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm, prospective, and open clinical phase II study. Methods: Information on 34 patients with stage IV osteogenic sarcoma treated with apatinib after failure of chemotherapy in Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2019 was collected and analyzed. The participants included 23 males and 11 females, with an average age of 35.24 years (11-73 years). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), PFS rate (PFR), and overall survival (OS) were evaluated. The treatment-related adverse events (AEs) and safety of apatinib were also evaluated. Results: Of the 34 patients, 33 were able to be evaluated for efficacy. One patient received apatinib treatment for less than one cycle; therefore, only safety analysis was performed. The 12-week clinical evaluation showed that 2 patients had a partial response (PR), 24 patients had stable disease (SD), and 7 patients had progressive disease (PD). The ORR, DCR, and PFR at 12 weeks were 6.06% (2/33), 78.79% (26/33), and 82%, respectively. By the end of the follow-up, 6 patients had SD (18.18%, 6/33), 27 patients had PD (81.82%, 27/33), and 15 patients died because of disease progression (45.45%, 15/33). The ORR was 0 (0/33), the DCR was 18.18% (6/33), and the median PFS (mPFS) was 7.89 months (95% CI: 4.56-11.21). The median OS (mOS) was 17.61 months (95% CI: 10.85-24.37). The most common treatment-related AEs were hand-foot syndrome (35.29%, 12/34), proteinuria (32.35%, 11/34), and hypertension (32.35%, 11/34). Conclusions: Apatinib is effective and well tolerated in stage IV osteogenic sarcoma patients after chemotherapy failure.

Keywords: Apatinib; osteogenic sarcoma; progression-free survival; safety.

Figure 1

Patient inclusion and exclusion flow chart.

Figure 2

Maximum and whole-course changes in sizes of target lesions vs. baseline after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy. (A) Maximum changes in sizes of target lesions vs. baseline after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy. (B) Whole-course changes in sizes of target lesions vs. baseline after apatinib treatment for stage IV osteogenic sarcoma that did not respond to chemotherapy.

Figure 3

Efficacy and toxicity of apatinib in stage IV oesteogenic sarcoma. (A) Overall responses of 33 patients with stage IV osteogenic sarcoma treated with apatinib. Among 33 patients, 31 had measurable lesions, and 2 patients had unmeasurable lesions. Responses at 12 weeks were PR in 2 (6.06%, 2/33), SD in 24 (72.73%, 24/33), and PD in 7 (21.21%, 7/33). (B) PFS after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy (mPFS: 7.89 months). (C) OS after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy (mOS: 17.61 months). (D) Frequencies and grades of adverse events to apatinib.

Figure 4

Comparison of imaging findings between 2 patients treated with apatinib for stage IV osteogenic sarcoma that did not respond to chemotherapy. (A-F) Efficacy in patients who were diagnosed with stage IV osteosarcoma at the first visit and received apatinib after they did not respond to first-line chemotherapy. (A, C, E) Imaging findings before treatment with apatinib (January 23, 2017). (B, D, F) Positron emission tomography-CT showed significant decreases in the sizes and metabolic activity of the tumors after treatment with apatinib (April 10, 2017). (G-H) Effects of apatinib in patients with metastatic Ewing’s sarcoma in the lungs who did not respond to first-line chemotherapy. (G) CT images of the chest before treatment with apatinib (May 25, 2017). (H) The lesions in the lungs remained stable from initiation of oral use of apatinib on May 25, 2017 to re-examination on November 24, 2017.