Ciccone Marcia A, Maoz Asaf, Casabar Jennifer K, Machida Hiroko, Mabuchi Seiji, Matsuo Koji
a Division of Gynecologic Oncology, Department of Obstetrics and Gynecology , University of Southern California , Los Angeles , CA , USA.
b Norris Comprehensive Cancer Center , University of Southern California , Los Angeles , CA , USA.
Expert Opin Investig Drugs. 2016 Jul;25(7):781-96. doi: 10.1080/13543784.2016.1181748. Epub 2016 May 13.
While serine-threonine kinases (STK) are attractive therapeutic targets in epithelial ovarian cancer, clinical outcomes of STK inhibitors in the management of recurrent disease have not been completely described.
A systematic literature review of published clinical studies on STK inhibitors targeting mTOR, MAPK, and aurora kinase pathways in recurrent epithelial ovarian cancer was conducted, revealing 18 clinical trials (497 patients). Pooled analyses were performed to assess treatment response, survival time, and adverse events. Median progression-free survival was 3.4 months in STK inhibitor-based therapy, and the average response rate and clinical benefit rate were 13% and 67%, respectively. Among regimens comprised of only STK inhibitors (11 trials, 299 patients), median progression-free time was 2.7 months, response rate was 10%, and clinical benefit rate was 64%. Compared to single STK inhibitor monotherapy (52.5%), clinical benefit rates significantly improved when STK inhibitors were combined with a cytotoxic agent (71.4%), other class biological agent (74.2%), or an additional STK inhibitor (95.0%) (all, P ≤ 0.002).
STK inhibitor-based therapy showed modest activity for recurrent epithelial ovarian cancer with reasonable clinical benefit rates, suggesting its potential utility for maintaining disease stability if supported by future studies. Efficacy appears greatly improved in appropriately selected patient populations, especially those with low-grade serous ovarian carcinoma, platinum-sensitive disease, cancers with somatic RAS or BRAF mutations, and when used in a combination regimen with a cytotoxic or biological agent.
虽然丝氨酸 - 苏氨酸激酶（STK）是上皮性卵巢癌中具有吸引力的治疗靶点，但STK抑制剂在复发性疾病管理中的临床结果尚未完全阐明。
对已发表的关于STK抑制剂靶向复发性上皮性卵巢癌中mTOR、MAPK和极光激酶通路的临床研究进行了系统的文献综述，共纳入18项临床试验（497例患者）。进行了汇总分析以评估治疗反应、生存时间和不良事件。基于STK抑制剂的治疗中，无进展生存期的中位数为3.4个月，平均缓解率和临床获益率分别为13%和67%。在仅由STK抑制剂组成的治疗方案中（11项试验，299例患者），无进展时间的中位数为2.7个月，缓解率为10%，临床获益率为64%。与单一STK抑制剂单药治疗（52.5%）相比，当STK抑制剂与细胞毒性药物（71.4%）、其他类生物制剂（74.2%）或另一种STK抑制剂（95.0%）联合使用时，临床获益率显著提高（均P≤0.002）。
基于STK抑制剂的治疗对复发性上皮性卵巢癌显示出适度的活性，临床获益率合理，这表明如果得到未来研究的支持，其在维持疾病稳定方面具有潜在效用。在适当选择的患者群体中，疗效似乎有很大改善，特别是那些低级别浆液性卵巢癌、铂敏感疾病、具有体细胞RAS或BRAF突变的癌症患者，以及与细胞毒性或生物制剂联合使用的联合治疗方案中。
