The efficacy and safety of immune checkpoint inhibitors in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis

Abstract

Background: We aim to assess the efficacy and safety profiles of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer using a meta-analysis.Methods: We extracted and examined data from phase I, II and III clinical trials from PubMed, Embase, Web of Science, and Cochrane Library, which included patients with metastatic castration-resistant prostate cancer who were treated with immune checkpoint inhibitors. We performed a meta-analysis to investigate several indexes of efficacy and safety, including the objective response rate, 1-year overall survival (OS) rate, prostate-specific antigen response rate, and adverse event rate of immune checkpoint inhibitors. The material data were calculated and pooled using The R Project for Statistical Computing and STATA 12.0 software.Results: We identified 12 clinical trials in our study. We assessed the pooled frequencies of all-grade AEs and grade ≥ 3 AEs first and showed 0.82 (95% CI: 0.74-0.91, I 2 = 94%, P < .01) and 0.42 (95% CI: 0.33-0.54, I 2 = 96%, P < .01), respectively. The objective response rate was 0.10 (95% CI: 0.04-0.19, I 2 = 70%, P < .01), and the 1-year OS and prostate-specific antigen response rate were 0.55 (95% CI: 0.45-0.67, I 2 = 93%, P < .01) and 0.18 (95% CI: 0.16-0.20, I 2 = 43%, P = .03), respectively. Conclusion:The immune checkpoint inhibitors therapy was well tolerated and showed potential to improve tumor responses in patients with metastatic castration-resistant prostate cancer.Abbreviations: ADT = androgen deprivation therapy, AEs = adverse events, AR = androgen receptor, dMMR = deficient mismatch repair, ICIs = Immune checkpoint inhibitors, CTLA-4 = cytotoxic T lymphocyte antigen 4, PD-1 = programmed death-1, PD-L1 = PD-1 ligand, mCRPC = metastatic castration-resistant PC, RCT = randomized controlled trial, MSI = microsatellite instability, ORR = objective response rate.

Efficacy and safety of immune checkpoint inhibitors for patients with prostate cancer: a systematic review and meta-analysis

“…cancer patients, respectively (83). Regarding PSAR, similar results were obtained; while the PSAR for Pembrolizumab monotherapy, Ipilimumab monotherapy, and Ipilimumab-plus-Nivolumab were 11%, 19%, and 14%, respectively in the mentioned study (83), it was 4.5%, 15.3%, and 13.6% for anti-PD-1/PD-L1 monotherapy, anti-CTLA-4 monotherapy, and anti-PD-1/PD-L1+anti-CTLA-4 regimen in accordance to our findings, respectively.…”

“…cancer patients, respectively (83). Regarding PSAR, similar results were obtained; while the PSAR for Pembrolizumab monotherapy, Ipilimumab monotherapy, and Ipilimumab-plus-Nivolumab were 11%, 19%, and 14%, respectively in the mentioned study (83), it was 4.5%, 15.3%, and 13.6% for anti-PD-1/PD-L1 monotherapy, anti-CTLA-4 monotherapy, and anti-PD-1/PD-L1+anti-CTLA-4 regimen in accordance to our findings, respectively. Although initial studies have proposed that immunotherapy with an autologous active cellular vaccine (Sipuleucel-T) provide promising outcomes for men with prostate cancer (84), the body of evidence came into the conclusion that prostate tumor is less immunogenic than thought before (85-87).…”

Research Progress in Target Cancer of Immune Checkpoint Inhibitors

“…Only two of the 14 patients with advanced mCRPC in the first trial of anti-CTLA-4 antibodies for PCa demonstrated a decrease in prostate-specific antigen (PSA) ≤50%. Subsequently, a clinical study expanded the number of mCRPC patients to 71 to test the difference in efficacy of Ipilimumab and radiotherapy combined with Ipilimumab [26]. 16% of patients in the highest dose group had a decrease in PSA of ≤50%, six had no progression, and one sustained a response.…”