Cao Qi, Bai Peng, Shi Deyao, Liao Jiali, Shi Hangchuan, Xing Yifei, Chen Ke, Zhang Xiaoping
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cancer Res Ther. 2020 Sep;16(5):990-1001. doi: 10.4103/jcrt.JCRT_295_18.
CYP17 inhibitors can block androgen production both intratumorally and systemically, thus attenuating the progression of prostate cancer (PCa). Many randomized controlled trials (RCTs) showed promising results that men with metastatic castration-resistant PCa (mCRPC) might benefit from treatment with CYP17 inhibitors such as abiraterone acetate and orteronel. The goal of this study was to evaluate the efficacy of CYP17 inhibitors for the prognosis in patients with mCRPC.
Studies were identified in PubMed/MEDLINE, the Cochrane Library, and the Web of Science. The RCTs with mCRPC patients focusing on the efficacy of CYP17 inhibitors were involved. Then, we analyzed the patients' prognosis such as overall survival (OS) and radiographic progression-free survival (RPFS).
A meta-analysis of the pooled data from seven randomized Phase III clinical trials was performed to compare 5516 mCRPC patients with CYP17 inhibitors versus that with placebo. Compared to placebo, the CYP17 inhibitors significantly increased the OS (pooled hazard ratios [HR]: 0.816, 95% confidence interval [CI]: 0.750-0.887), RPFS (pooled HR: 0.647, 95% CI: 0.557-0.752), and time to prostate-specific antigen (PSA) progression (pooled HR: 0.599, 95% CI: 0.517-0.693). Additional endpoints such as PSA response rate, objective response assessed by Response Evaluation Criteria in Solid Tumors, and time to initiation of chemotherapy were included in this study and were found having significant improvement with CYP17 inhibitors compared to placebo.
This research showed that CYP17 inhibitors had a significant improvement on prognosis of patients with mCRPC within a relative safety profile both in pre- and post-chemotherapy trials. These expected results provide evidence for the use of CYP17 inhibitors to treat mCRPCs.
CYP17抑制剂可在肿瘤内和全身阻断雄激素生成，从而减缓前列腺癌（PCa）的进展。许多随机对照试验（RCT）显示了有前景的结果，即转移性去势抵抗性PCa（mCRPC）患者可能从醋酸阿比特龙和奥替诺隆等CYP17抑制剂治疗中获益。本研究的目的是评估CYP17抑制剂对mCRPC患者预后的疗效。
在PubMed/MEDLINE、Cochrane图书馆和科学网中检索研究。纳入聚焦CYP17抑制剂疗效的mCRPC患者的RCT。然后，我们分析了患者的预后，如总生存期（OS）和影像学无进展生存期（RPFS）。
对来自7项随机III期临床试验的汇总数据进行荟萃分析，以比较5516例接受CYP17抑制剂治疗的mCRPC患者和接受安慰剂治疗的患者。与安慰剂相比，CYP17抑制剂显著提高了OS（汇总风险比[HR]：0.816，95%置信区间[CI]：0.750 - 0.887）、RPFS（汇总HR：0.647，95%CI：0.557 - 0.752）以及前列腺特异性抗原（PSA）进展时间（汇总HR：0.599，95%CI：0.517 - 0.693）。本研究还纳入了其他终点，如PSA缓解率、实体瘤疗效评价标准评估的客观缓解率以及开始化疗的时间，结果发现与安慰剂相比，CYP17抑制剂在这些方面有显著改善。
本研究表明，在化疗前和化疗后的试验中，CYP17抑制剂在相对安全的情况下对mCRPC患者的预后有显著改善。这些预期结果为使用CYP17抑制剂治疗mCRPC提供了证据。
