Efficacy of PARP inhibitors in patients with metastatic castration resistant prostate carcinoma: A meta-analysis of phase III randomized controlled trials.

person Rushin Patel Community Hospital of San Bernardino, San Bernardino, CA info_outline Rushin Patel, Mosunmoluwa Oyenuga, Afoma Onyechi, Akshit Chitkara, Sara Sartaj, Mohamed G Mohamed, Zalak Patel, Mrunal Patel

Authors person Rushin Patel Community Hospital of San Bernardino, San Bernardino, CA info_outline Rushin Patel, Mosunmoluwa Oyenuga, Afoma Onyechi, Akshit Chitkara, Sara Sartaj, Mohamed G Mohamed, Zalak Patel, Mrunal Patel Organizations Community Hospital of San Bernardino, San Bernardino, CA, Abbott Northwestern Hospital, Minneapolis, SSM St Mary's hospital, St Louis, MO, University of California Riverside, Riverside, CA, SSM St Mary's Hospital, Richmond Heights, MO, SSM St Louis University hospital, St Louis, MO, Trumbull Regional Medical Center, Western Reserve, Warren, OH Abstract Disclosures Research Funding No funding received None. Background: PARP inhibitors effectively treat several solid tumors, regardless of the presence of BRCA mutations. Patients with castration-resistant metastatic prostate cancer become refractory to androgen deprivation therapy. PARP inhibitors were recently approved for use in prostate cancer, and have opened new avenues in prostate cancer treatment research. Methods: We systematically searched multiple databases using pre-specified search terms. We included only phase III RCTs comparing PARP inhibitors versus standard of care in patients with castration-resistant biopsy-proven metastatic prostate cancer. The outcomes studied were radiologically guided progression-free survival (PFS) and overall survival (OS). We used a random effects model via RevMan 5.4 software for statistical analysis. Results: 3 phase III RCTs met the inclusion criteria with a total of 1606 patients (PARP inhibitors = 867 patients, standard of care = 739 patients). Compared to the standard of care, PARP inhibitors showed significantly higher PFS [HR = 0.62( 95% CI, 0.49-0.78) P < 0.0001]. There was no statistically significant difference in OS [HR = 0.85( 95% CI, 0.69-0.1.04) P = 0.11] between the two groups. Conclusions: The use of PARP inhibitors in patients with castration-resistant metastatic prostate cancer is associated with improved progression-free survival. No significant difference was observed in overall survival between the two groups. There is a need to study the cost-benefit analysis of using PARP inhibitors as they do not show any improvement in overall survival. Trial name PROFOUND trial (de Bono et al) MAGNITUDE trial (Chi et al) PROPEL trial (Clarke et al) National Clinical Trial number NCT02987543 NCT03748641 NCT03732820 Year of study published 2020 2022 2022 Population studied Metastatic castration-resistant prostate cancer Metastatic castration resistant prostate cancer with and without homologous recombination repair (HRR) gene alterations Metastatic castration-resistant prostate cancer Treatment groups Olaparib versus Second-generation hormonal therapy (physician's choice of Abiraterone or Enzalutamide) Niraparib + AAP (Abiraterone acetate plus Prednisone) versus Placebo + AAP (Abiraterone acetate plus Prednisone) Olaparib + Abiraterone versus Placebo + Abiraterone Number of participants E = 256 C = 131 Total = 387 E = 212 C = 211 Total = 423 E = 399 C = 397 Total = 796 Progression free survival (Hazard ratio for disease progression or death) 0.49(95% CI, 0.38-0.63) P < 0.001 0.73 (95% CI, 0.56-0.96) P = 0.0217 0.66 (95% CI, 0.54 to 0.81) P < 0.001 Overall survival (Hazard ratio for death) 0.55 (95% CI, 0.29 to 1.06) P = 0.074 0.94 (0.65-1.36) P = 0.73 0.86; 95% CI, 0.66 to 1.12; P = 0.29 E = Exposure group (PARP inhibitors) C = Control group.

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