Deshpande H A, Cecchini M, Ni Choileain S, Jones R
Yale Cancer Center, Smilow Cancer Hospital,New Haven, Connecticut, USA.
Yale University, New Haven, Connecticut, USA.
Drugs Today (Barc). 2017 Apr;53(4):247-255. doi: 10.1358/dot.2017.53.4.2560077.
Soft tissue sarcoma represents about 1% of all solid malignancies. The standard chemotherapy regimens have included doxorubicin alone or in combination with other agents. Despite recent advances in treatment beyond first line - with the FDA approval of pazopanib, eribulin and trabectidin - overall survival for patients with metastatic disease remains in the region of 12-19 months. Olaratumab is a monoclonal antibody directed against platelet-derived growth factor receptor alpha (PDGFRalpha). It was studied in a phase Ib and randomized phase II study in combination with doxorubicin in patients with soft tissue sarcoma who previously had not received doxorubicin for metastatic disease. The results of the phase II study showed a statistically significant improvement in progression-free survival up to 6 months, and a more dramatic improvement in overall survival to 26.9 months. This is the first randomized trial to show a significant improvement in overall survival compared to doxorubicin alone. An ongoing phase III study has completed accrual and results are being analyzed. Olaratumab has been granted accelerated approval by the United States Food and Drug Administration. Ongoing trials are underway to further demonstrate the mechanism of action. This review will document the studies involved in the development of olaratumab in the treatment of soft tissue sarcomas.
软组织肉瘤约占所有实体恶性肿瘤的1%。标准化疗方案包括单独使用阿霉素或与其他药物联合使用。尽管一线治疗取得了最新进展——帕唑帕尼、艾瑞布林和曲贝替定已获美国食品药品监督管理局（FDA）批准——但转移性疾病患者的总生存期仍在12至19个月左右。奥拉单抗是一种针对血小板衍生生长因子受体α（PDGFRα）的单克隆抗体。在一项Ib期和随机II期研究中，对先前未接受过阿霉素治疗转移性疾病的软组织肉瘤患者，将奥拉单抗与阿霉素联合使用进行了研究。II期研究结果显示，无进展生存期在长达6个月时具有统计学意义的改善，总生存期有更显著改善，达到26.9个月。这是首个显示与单独使用阿霉素相比总生存期有显著改善的随机试验。一项正在进行的III期研究已完成入组，结果正在分析中。奥拉单抗已获得美国食品药品监督管理局的加速批准。正在进行的试验正在进一步证明其作用机制。本综述将记录奥拉单抗治疗软组织肉瘤的研发过程中涉及的研究。
