Abstract
e17053 Background: Recent therapeutic advances in prostate cancer have allowed patients with metastatic disease to live longer and better, especially in the castration sensitive setting. Although improvements have been observed in the castration resistant space, survival in this setting remains suboptimal. Early-phase clinical trials suggest the combination of PARP inhibitors (PARPi) and immune checkpoint inhibitors (ICI) have synergistic effect by modulating the tumor microenvironment. In this systematic review and meta-analysis, we assessed the efficacy and safety of PARPi and ICI in the metastatic castration-resistant prostate cancer (mCRCP) setting. Methods: Pubmed, Cochrane and EMBASE were systematically searched from inception through December 10, 2023. Randomized and non-randomized clinical trials evaluating PARPi + ICI in mCRPC were included. PSA response rate (PSArr), radiographic progression-free survival (rPFS), objective response rate (ORR) and overall survival (OS) were analyzed. Subgroups according to (HRR) were assessed. We also pooled the prevalence of immune-related adverse events (irAE) and their corresponding 95% confidence intervals (95% CI). Statistical analysis was performed using R software version 4.3.2 and heterogeneity was evaluated through I2 statistics. Results: We screened 1070 reports, and six trials met the inclusion criteria (one phase III RCT and 5 phase I/II non-RCT), involving 799 participants. The overall ORR was 8.48% (95% CI 6.48-10.86 I2 0%). About 19% of patients achieved an PSArr (95% CI 9.51-32.50 I2 75%). Median OS was 15.8 months (95% IC 13.9-15.8), and rFPS was 4.5 months (95% IC 4.4-4.9). In patients harboring HRR mutations, PSArr was 17.53% (95% CI 10.43-27.95 I2 75), while in HRR non-mutated it was 10.49% (95% CI 5.89-17.99 I2 0%). The frequency of any-grade irAEs was 21.12% (95% CI 12.34-33.74 I2 85%), with 6.70% of grade 3-4 irAEs (95% CI 3.09-13.91 I2 80%). Hypothyroidism rate was 8.53% (95% CI 5.86-12.27 I2 29%) and adrenal insufficiency was 2.80% (95% CI 1.81-4.30 I2 0%). Conclusions: This meta-analysis results suggest that the combination of PARPi plus ICI in patients with mCRPC is safe and may benefit mainly patients with HRR mutations. Further studies in biomarker selected patients are needed. [Table: see text]
Published Version
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