Treatment outcomes for metastatic castration-resistant prostate cancer (mCRPC) following progression on upfront androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPI) for metastatic castration-sensitive prostate cancer (mCSPC).

Abstract

60 Background: Combined ADT and ARPI is associated with improved overall survival (OS) compared with ADT alone in patients with mCSPC. The activity of subsequent therapies for mCRPC is not well characterized. Methods: We conducted a retrospective analysis of patients enrolled on a biobank at 6 cancer centres in British Columbia, Canada. Patients who received abiraterone or apalutamide for mCSPC were included. Data including baseline clinical prognostic factors and clinical outcomes (per Prostate Cancer Working Group III) were collected from patient records. Survival was analyzed by Kaplan-Meier method and Log Rank test and prognostic variables were determined using Cox regression. Results: 168 patients were identified of which 126 (75%) received abiraterone, 38 (23%) received apalutamide, and 4 (2%) received one ARPI and switched to the other for toxicity. Median age was 69 years and Gleason score ≥ 8 in 61%. Site of metastasis (mets) at mCSPC was lymph node (n=91), bone (n=141), and liver (n=6). As of August 28 2021, a total of 46 patients progressed to mCRPC, of which 38 received subsequent systemic therapy. First-line mCRPC treatments were docetaxel (n=12), Radium-223 (10), enzalutamide (6), platinum chemotherapy (3), and others (7) including immune checkpoint inhibitors (1) and Lutetium177-PSMA-617 (1) and other investigational agents (5). Outcomes are shown in the table. On univariate Cox analysis, clinical factors at time of mCRPC associated with worse OS were: LDH above upper limit of normal (HR 5.0, 95% CI 1.7-14.5), hemoglobin below lower limit of normal (5.2, 1.1-23.8), presence of ≥ 20 bone mets (3.7, 1.4-9.8), and increasing PSA (1.002, 1.001-1.003). Conclusions: PSA decline rates and survival are modest for patients who have progressed following upfront abiraterone or apalutamide plus ADT for mCSPC. Further follow-up is required to accurately determine outcomes with current mCRPC standard therapies following up-front ADT+ ARPI. Recently approved treatment options such as Lutetium177-PSMA-617 and PARP inhibitors for DNA damage repair deficient tumors may help to improve outcomes for these patients.[Table: see text]