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A Systematic Review of the Emerging Role of Immune Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer: Will Combination Strategies Improve Efficacy?

Heidegger, I; Necchi, A; Pircher, A; Tsaur, I; Marra, G; Kasivisvanathan, V; Kretschmer, A; ... EAU-YAU Prostate Cancer Working Party; + view all (2020) A Systematic Review of the Emerging Role of Immune Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer: Will Combination Strategies Improve Efficacy? European Urology Oncology 10.1016/j.euo.2020.10.010. (In press). Green open access

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Abstract

Context: The role of immune checkpoint inhibition (ICI) in the treatment of prostate cancer (PC) still remains elusive. It has been proposed that combination of ICI with other molecules increases the efficacy of immunotherapy in PC. Objective: To systematically review the literature to assess the potential role of ICI in combination with additional therapies for the management of metastatic castration-resistant PC (mCRPC). Evidence acquisition: A systematic review using Medline and scientific meeting records was carried out in September 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Ongoing trials of immunotherapy with standard mCRPC therapeutics were identified via a systematic search on ClinicalTrials.gov. Evidence synthesis: A total of five full-text papers, ten congress abstracts, and 15 trials on ClinicalTrials.gov were identified. Preclinical evidence suggests that combinational approaches might be considered to enhance the efficacy of ICI in PC patients. This led to the design of more than 50 immunotherapy-based clinical trials. The majority of the studies focus on ICI combinations with vaccines, androgen deprivation therapy, chemotherapy, PARP inhibition, radiotherapy, and prostate-specific membrane antigen–guided radioligand therapy. Preliminary analyses reported promising findings for the use of ICI in combination with other anticancer therapies. However, no phase 3 trial has yet reported final results, so no level 1 evidence with long-term outcomes currently supports the combination of ICI with mCRPC therapies. Conclusions: Preclinical and clinical trials have demonstrated that combining immunotherapy with standard mCRPC treatment options has the potential to provide a synergistic effect. Nonetheless, a better understanding of the mechanism and of the optimal treatment approach is still needed. Patient summary: We reviewed the literature on immunotherapy in combination with standard treatments for patients with metastatic castration-resistant prostate cancer (mCRPC). Current evidence supports the hypothesis that immunotherapeutic drugs might be effective in mCRPC if combined with other treatment options. However, results of ongoing trials are still awaited before this novel treatment approach can be implemented in the daily practice.

Type: Article
Title: A Systematic Review of the Emerging Role of Immune Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer: Will Combination Strategies Improve Efficacy?
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.euo.2020.10.010
Publisher version: https://doi.org/10.1016/j.euo.2020.10.010
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Combination therapies, Immunotherapy, Metastatic castration-resistant prostate cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10120099
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