Real-world evaluation of olaparib combined with novel hormone therapy in metastatic castration-resistant prostate cancer with intraductal adenocarcinoma.

Abstract

213 Background: Intraductal adenocarcinoma of the prostate (IDC-P) is an aggressive histological variant of prostate cancer and was reported harboring increased homologous recombination repair deficiency (HRD). Our aim was to explore the predictive value of IDC-P on the efficacy of novel hormone therapy (NHT) in combination with olaparib in the metastatic castration-resistant prostate cancer (mCRPC) after progression on NHT. Methods: This study included 64 consecutive patients receiving olaparib plus NHT (abiraterone (59), enzalutamide (3), darolutamide (2)) after progression on NHT: 33 IDC-P and 31 prostate adenocarcinoma (PAC) were identified. Prostate-specific antigen (PSA) progression-free survival (PSA-PFS), treatment change-free survival (TFS), and overall survival (OS) were compared between IDC-P and PAC using the Kaplan-Meier method. Cox proportional-hazards models were employed to evaluate the predictive value of IDC-P for PSA-PFS, TFS, and OS. PSA response, subgroup analysis, and adverse events (AEs) were also evaluated. Results: The median follow-up for the total cohort was 35 months. Patients with IDC-P presented longer PSA-PFS and TFS compared to those with PAC (PSA-PFS: 6.2 months (IDC-P) vs. 3.0 months (PAC), p < 0.01; TFS: 10.0 months (IDC-P) vs. 6.3 months (PAC), p < 0.01). The PSA response rate was comparable (45.2% (IDC-P) vs. 35.7% (PAC), p = 0.60). In patients with BRCA 1/2 variants, IDC-P was associated with a significantly longer PSA-PFS and TFS (PSA-PFS: 9.8 months (IDC-P) vs. 3.0 months (PAC), p < 0.01; TFS: 11.3 months (IDC-P) vs. 10.2 months (PAC), p = 0.04). In the BRCA 1/2 wild-type/unknown subgroup, patients with IDC-P showed comparable PSA-PFS and TFS (PSA-PFS: 3.7 months (IDC-P) vs. 3.0 months (PAC), p = 0.27; TFS: 4.0 months (IDC-P) vs. 5.2 months (PAC), p = 0.20). Multivariate Cox regression analysis demonstrated IDC-P to be a predictor for better PSA-PFS and TFS independent of BRCA 1/2 variation. OS was comparable in the total cohort but displayed benefits in IDC-P when no further treatments were administered following olaparib plus NHT (14.0 months (IDC-P) vs. 10.2 months (PAC), p = 0.035). AE rates were comparable between IDC-P and PAC. Conclusions: IDC-P predicted better efficacy of olaparib plus NHT in previously NHT-treated mCRPC independent of BRCA1/2 mutation status. The results identifies a population who may benefit from poly ADP-ribose polymerase inhibitors combined with NHT without using genomic testing.