Cren Pierre-Yves, Lebellec Loïc, Ryckewaert Thomas, Penel Nicolas
Lille University, Medical School, Lille, France.
Medical Oncology Unit, Tourcoing Hospital, Tourcoing, France.
Front Oncol. 2020 Nov 24;10:594445. doi: 10.3389/fonc.2020.594445. eCollection 2020.
We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.
我们回顾了所有已完整发表的评估抗血管生成药物治疗肉瘤患者的临床试验(上一期,2020年1月13日)。抗血管生成大分子(如贝伐单抗或奥布替尼)的疗效令人失望。许多多激酶抑制剂已在样本量有限且未根据组织学亚型分层的非随机II期试验中进行评估,因此对此类试验的解读极具挑战性。相反,帕唑帕尼、瑞戈非尼和索拉非尼已通过双盲安慰剂对照随机II期或III期试验进行评估。与安慰剂相比,索拉非尼在韧带样型纤维瘤病患者中显示出活性。基于3期试验结果,帕唑帕尼已获批用于治疗经治的非脂肪细胞性软组织肉瘤。瑞戈非尼目前正在多个临床环境中进行评估,并在经治的非脂肪细胞性软组织肉瘤和晚期经治骨肉瘤中显著改善了无进展生存期。多激酶抑制剂是肉瘤治疗的一项突破。许多试验正在进行中。然而,预测因素仍然缺失。