Efficacy and safety of interventions for metastatic castration resistant prostate cancer (mCRPC) patients progressing on androgen receptor-axis-targeted (ARAT) therapy: a systematic literature review.

Background: To review the literature to outline findings from clinical trials assessing interventions for metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on androgen receptor-axis-targeted (ARAT) therapies.

Methods: A systematic literature review was performed to identify trials that assessed the efficacy and safety of interventions used in patients that progressed on prior ARAT therapies. A literature search was conducted using the OVID platform that searched the EMBASE, MEDLINE, and CENTRAL bibliographic databases.

Results: Of the 10,114 citations identified, a total of 36 studies representing 33 unique trials were included in the review. Of the 33 trials, 21 were randomized controlled trials and 12 were single-arm trials. A total of 11 were phase III trials, 13 were phase II trials, and 2 were phase I trials. The majority of included trials were open-label (n = 29) and the remaining were double-blind (n = 4). A total of 16 trials evaluated ARAT based therapies, 7 trials evaluated taxane-based treatments, 10 trials evaluated PARP inhibitors, 8 trials evaluated immunotherapies, and 8 trials evaluated other therapies (i.e. cabozantinib, mitoxantrone, radium-223,¹⁷⁷[Lu-177]-PNT2002,¹⁷⁷Lu-PSMA-617, samotolisib).

Conclusions: This systematic review demonstrated there are limited effective treatment options in this patient population. Unlike other cancer types, immunotherapy agents appear to provide little to no benefit. Conversely, agents such as taxane-based chemotherapy (e.g. cabazitaxel) and radionuclide therapy provide the most value in this patient population. Further research is needed to explore new therapies in this disease area and to optimize existing treatment strategies with more effective combination therapies.