CYP17 inhibitors improve the prognosis of metastatic castration-resistant prostate cancer patients: A meta-analysis of published trials

J Cancer Res Ther. 2020 Sep;16(5):990-1001. doi: 10.4103/jcrt.JCRT_295_18.

Abstract

Background and aims: 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.

Materials and methods: 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).

Results: 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.

Conclusion: 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.

Keywords: CYP17; meta-analysis; metastatic castration-resistant prostate cancer; prognosis.

Publication types

  • Meta-Analysis

MeSH terms

  • Abiraterone Acetate / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Cytochrome P-450 Enzyme Inhibitors / therapeutic use*
  • Humans
  • Male
  • Prognosis
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Randomized Controlled Trials as Topic
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Survival Rate

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Steroid 17-alpha-Hydroxylase
  • Prostate-Specific Antigen
  • Abiraterone Acetate