Guo Quan, Yang Qing, Li Jun, Liu Guipeng, Nikoulin Igor, Jia Steve
Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China.
Research and Development, IriSys, LLC. San Diego, CA 92121, United States.
Curr Pharm Biotechnol. 2018;19(14):1114-1121. doi: 10.2174/1389201020666181226123054.
Epithelial ovarian cancer (EOC) is one of the most common cancers in the female reproductive system and deadliest gynecological cancer in the United States. Standard treatments by surgery and platinum-based chemotherapy are not satisfied for the patients with high risk of relapse. Advances in molecular biology for EOC development have brought several targeted therapies to benefit recurrent patients. Poly-ADP-ribose polymerase inhibitors (PARPi) may be one of the most successful classes of targeted therapies with three approved medicines. For better clinical outcomes and more comprehensive disease management of EOC, more novel classes of targeted therapies are needed.
We focus on non-PARPi novel targeted therapies that are completed or on-going in phase III clinical trials by searching databases of Pubmed and Clinicaltrials.gov. Keywords of "ovarian cancer, targeted therapy and phase III trial" were used for publications and information from May 2012 to May 2018.
There are total 150 viable EOC phase III studies listed in Clinicaltrials.gov., including 20 completed studies with results and 73 on-going studies. Bevacizumab plus chemotherapy is the only medication with government approval for recurrent EOC. Targeted therapies against other growthrelated factors, cytokines and folate receptor are failed in phase III trials or still on-going.
Implications of on-going phase III trials are: 1) combination therapy of bevacizumab with atezolizumab may be the most anticipated studies for approvals; 2) mirvetuximab soravtansine plus chemotherapy may generate positive results to justify an approval; and 3) Immune therapy for EOC may bring new treatments for the patients.
上皮性卵巢癌（EOC）是女性生殖系统中最常见的癌症之一，也是美国最致命的妇科癌症。手术和铂类化疗的标准治疗方法对于复发风险高的患者并不令人满意。EOC发展的分子生物学进展带来了几种靶向治疗方法，使复发患者受益。聚ADP核糖聚合酶抑制剂（PARPi）可能是最成功的靶向治疗类别之一，有三种已获批药物。为了获得更好的临床结果和对EOC进行更全面的疾病管理，需要更多新型的靶向治疗方法。
我们通过搜索PubMed和Clinicaltrials.gov数据库，重点关注已完成或正在进行III期临床试验的非PARPi新型靶向治疗方法。使用“卵巢癌、靶向治疗和III期试验”的关键词来检索2012年5月至2018年5月的出版物和信息。
Clinicaltrials.gov上总共列出了150项可行的EOC III期研究，包括20项已完成并公布结果的研究和73项正在进行的研究。贝伐单抗联合化疗是唯一获得政府批准用于复发性EOC的药物。针对其他生长相关因子、细胞因子和叶酸受体的靶向治疗在III期试验中失败或仍在进行中。
正在进行的III期试验的意义在于：1）贝伐单抗与阿替利珠单抗的联合治疗可能是最值得期待获批的研究；2） mirvetuximab soravtansine联合化疗可能产生阳性结果以证明获批合理；3）EOC的免疫治疗可能为患者带来新的治疗方法。
