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.
Implications for practice: For advanced osteosarcoma progressing upon chemotherapy, antiangiogenesis tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging the progression-free survival in previous multicenter trials and have been included into new National Comprehensive Cancer Network guidelines as second-line therapy. Apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2, which is domestically made in China. This phase II trial supports the use of apatinib in patients with advanced osteosarcoma progressing after chemotherapy.
摘要
背景。抗血管生成酪氨酸激酶抑制剂 (TKI) 已被证明可以在治疗晚期骨肉瘤时延长无进展生存期 (PFS)。甲磺酸阿帕替尼是一种可以特异性抑制血管内皮生长因子受体‐2 的 TKI。我们旨在于对经过化疗后出现疾病进展的晚期高级别骨肉瘤患者进行阿帕替尼评估。
材料和方法。本次 II 期试验于北京大学人民医院进行。我们招募了出现进展性复发或不可切除骨肉瘤的参与者(年龄 ≥16 岁)。根据体表面积的不同，参与者们每天服用一次 750 mg 或 500 mg 的阿帕替尼，直至出现疾病进展或不可接受的毒性。主要终点为客观缓解率和 4 个月 PFS。
结果。最终，我们一共将 37 名参与者纳入分析。直到最终随访时，客观缓解率(完全缓解 + 部分缓解)为 43.24% (16/37)。4 个月 PFS 率为 56.76% [95% 置信区间 (CI)，39.43%–70.84%]。中位 PFS 和总生存期分别为 4.50 个月(95% CI，3.47–6.27)和 9.87 个月(95% CI，7.97–18.93)。毒性作用导致 37 名患者中的 25 名患者 (67.57%) 出现剂量减少或试验中断。最常见的 3–4 级不良反应如下:6 名患者 (16.22%) 出现气胸，4 名患者 (10.81%) 出现伤口裂开，3 名患者 (8.11%) 出现蛋白尿，3 名患者 (8.11%) 出现腹泻，以及 3 名患者 (8.11%) 出现手足综合征。在试验期间未报告其他重度不良反应。无治疗相关的死亡。
结论。阿帕替尼是一种治疗晚期骨肉瘤的敏感药物，在化疗失败后的缓解率较高，与其他 TKI 相比，具有相似的反应持续时间。
实践意义:对于经过化疗后出现疾病进展的晚期骨肉瘤，抗血管生成酪氨酸激酶抑制剂 (TKI) 在先前的多中心试验中已被证明可以有效地延长无进展生存期，并已作为二线治疗被收录在全新的国家综合癌症网络指南之中。阿帕替尼是一种在中国生产的可以特异性抑制血管内皮生长因子受体‐2 的 TKI。本次 II 期试验支持在经过化疗后出现疾病进展的晚期骨肉瘤患者中使用阿帕替尼。
Keywords: Apatinib; Metastasis; Osteosarcoma; Refractory to chemotherapy; Unresectable.
© AlphaMed Press 2018.