Cross resistance among novel androgen receptor axis-targeted agents in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.

395 Background: Previous studies reported a cross resistance among novel androgen receptor axis-targeted agents (ARATs) in patients with metastatic castration-resistant prostate cancer. However, the effects of sequential therapy with novel ARATs in non-metastatic castration-resistant prostate cancer (nmCRPC) remain unclear. Methods: This multi-institutional retrospective study included 56 patients with nmCRPC treated with second-novel ARATs after first-novel ARATs treatments, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate between January 2014 and April 2024. The duration of novel ARATs treatment and PSA response were compared between first-use and second-use of novel ARATs. Results: The median age at nmCRPC diagnosis were 76 years. Of the 56 patients, 14 (25%), 16 (29%), 11 (20%), and 16 (29%) were treated with apalutamide, enzalutamide, darolutamide, and abiraterone acetate as second-novel ARATs. Median duration of novel ARATs treatment in second-use was significantly shorter than that in first-use (7.0 month vs. 14 month, respectively, P = 0.038). The rates of PSA decline ≥50% and ≥90% in second-use were significantly lower than those in first-use (25% vs. 73%, P < 0.001; 9.1% vs. 36%, P = 0.004; respectively). The rate of patients who did not achieve any PSA response in second-use was significantly higher than that in first-line use (45% vs. 11%, P < 0.001). Conclusions: A significant cross resistance among novel ARATs was observed in patients with nmCRPC. A further study is needed to evaluate the optimal candidates for sequential therapy with novel ARATs.