Clinical outcomes with systemic therapy given after progression on prostate specific membrane antigen radioligand therapy (PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

78 Background: PSMA-RLT is a novel therapeutic modality that improves overall survival in mCRPC. However, outcomes for systemic therapy given after progression on PSMA-RLT are not well described. We investigated treatment choices and outcomes in patients (pts) with mCRPC who experienced disease progression after PSMA-RLT. Methods: We performed a single center retrospective cohort study of pts with mCRPC, who received PSMA-RLT at the Jewish General Hospital between 2020 and 2023. Clinical characteristics, PSA50, further lines of therapy post PSMA-RLT and survival were abstracted from chart review. A log-rank test was used to assess overall survival (OS). Post-PSMA-RLT specific OS (Post-RLT-OS) was defined from the date of first systemic treatment after PSMA-RLT failure to death or last follow up. Results: We identified 42 pts who received PSMA-RLT for mCRPC. The median age was 63 years (47-89) and the majority (56.1%) of pts received PSMA-RLT as a 3rd or later line of therapy in mCRPC setting. Amongst these pts, 15/42 (35.7%) achieved a PSA50 response to PSMA-RLT; 36 pts experienced disease progression, and 25/36 with disease progression (69.4%) received subsequent active systemic therapy. Post-PSMA-RLT systemic therapy included chemotherapy (n=17), PARP inhibitors (PARPi) (n=3), bipolar androgen therapy (BAT) followed by androgen receptor-axis targeted agent (ARAT) (BAT+ARAT) (n=2), Radium (n=2), BAT (n=1), and different PSMA-RLT agent (n=1). Amongst the pts who received post-PSMA-RLT therapy, 5/25 (20%) achieved a PSA50 response. PSA50 responses were observed in pts who received chemotherapy (n=2), BAT+ARAT (n=2) and PARPi (n=1). After a median follow-up of 10 months, the median Post-RLT-OS in the entire cohort was 11.7 months. Post-RLT-OS was significantly associated with PSA levels at the time of post-PSMA-RLT systemic therapy. The median Post-RLT-OS for pts with PSA < 100 (n=11), 100 ≤ PSA < 1000 (n=5) PSA ≥ 1000 (n=5) was 15, 15.7, and 8.6 months respectively (P = 0.014). Conclusions: Some pts derive benefit from post-PSMA-RLT systemic therapy; however, the overall response rate is low and therapeutic options are limited. More research is needed to define mechanisms of resistance to PSMA-RLT, and to identify novel therapeutic opportunities in this patient population.