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

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. In addition, exploratory analyses were conducted to identify potential biomarkers or characteristics for predicting the prognoses of patients with mCRPC receiving combination therapy. 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 1 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. Exploratory analysis identified pretreatment prostate-specific antigen levels as prognostic biomarkers for patients with mCRPC undergoing combination therapy with PD-1 inhibitors and PARPi. In addition, homologous recombination repair mutations were identified as molecular biomarkers for OS of patients with mCRPC treated with combination therapy. 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. Furthermore, pretreatment prostate-specific antigen levels and homologous recombination repair mutations have been identified as potential prognostic biomarkers in patients with mCRPC receiving combination therapy.