Clinical evaluation of combined programmed cell death protein 1 inhibitor and poly(ADP-ribose) polymerase inhibitor in metastatic castration-resistant prostate cancer patients: Insights from a real-world study

Abstract

Background: This study aimed to evaluate the clinical efficacy and safety of combining a programmed cell death protein 1 (PD-1) inhibitor with a poly(ADP-ribose) polymerase inhibitor (PARPi) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after multiple lines of treatment, from a real-world perspective.

Materials and methods: This open-label, single-arm, prospective study enrolled patients with mCRPC who had experienced disease progression after docetaxel and at least 2 lines of next-generation hormonal agents to receive camrelizumab (PD-1 inhibitor) and fluzoparib (PARPi). The primary endpoints were radiographic progression-free survival and overall survival (OS), and the secondary endpoints were prostate-specific antigen progression-free survival and safety.

Results: Eight patients with mCRPC who met the inclusion criteria were enrolled. The results showed that the median radiographic progression-free survival was 5.1 months, the median OS was 8.1 months, and the median prostate-specific antigen progression-free survival was 3.1 months. Safety analysis revealed that 87.5% of the patients experienced one or more treatment-related adverse events (AEs), with 37.5% reporting grade 3 or higher treatment-related AEs. None of the patients discontinued treatment because of treatment-related AEs.

Conclusions: This real-world study demonstrated that the combination of a PD-1 inhibitor and PARPi exhibited sustained antitumor activity with an acceptable safety profile in the fourth-line treatment of patients with mCRPC.

Keywords

Metastatic castration-resistant prostate cancer / Poly(ADP-ribose) polymerase inhibitor / Programmed cell death protein 1 inhibitor / Real-world study / Biomarker

Acknowledgments

None.

Statement of ethics

The study was conducted in accordance with the Declaration of Helsinki and its subsequent revisions and was approved by the ethics committee of The Second Hospital of Tianjin Medical University (approval number: 2021-001). This clinical trial was registered with the Chinese Clinical Trial Registry under the registration number ChiCTR2100043664. Written informed consent was obtained from all participants prior to study initiation.

Conflict of interest statement

YW is a member of editorial board of Current Urology and confirms no involvement in any stage of this article's review process, ensuring unbiased editorial decision making. The other authors declare no conflicts of interest.

Funding source

This work was supported by the National Natural Science Foundation of China (grant numbers 82273262 and 81872078), the Tianjin Health Science and Technology Project (grant number TJWJ2024XK007), the Natural Science Foundation of Tianjin (grant number 21JCYBJC01430), Key Program of Tianjin Municipal Education Commission (grant number 2022ZD071), Tianjin Health Research Project (grant number TJWJ2023MS006), Tianjin Institute of Urology Funding Program (grant number MYSRC202315), Tianjin Health Research Project (grant number TJWJ2023XK008), and Scientific Research Program of Tianjin Municipal Education Commission (grant number 2023KJ022).

Data availability

The original data presented in this study are included in the article and supplementary material. Further inquiries should be directed to the corresponding authors.

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