Abiraterone with discontinuation of gonadotropin-releasing hormone (GnRH) analogues in patients (pts) with metastatic prostate cancer (PC): Survival results from a single-arm, phase II study.

e17044 Background: Abiraterone acetate (AA) is a CYP17 inhibitor, an enzyme required for androgen biosynthesis. AA is an approved first-line treatment for metastatic PC (mPC). A first-in-human trial demonstrated inadequate testosterone (T) suppression with AA monotherapy, leading to its subsequent development in combination with GnRH analogues. We conducted a single arm, phase II trial of pts with mPC treated with AA+Prednisone (AAP) following the discontinuation of GnRH therapy. We previously reported on the primary endpoint, demonstrating successful suppression of T levels with AA monotherapy. This report presents results on the time to luteinizing hormone (LH) normalization and survival outcomes. Methods: We conducted a single arm, phase II study for pts with mPC treated with AAP following GnRH analogue discontinuation. Primary endpoint of T suppression was reported previously. Secondary endpoints included time-to-LH normalization, progression-free survival (PFS) and overall survival (OS). Adverse events were monitored throughout the trial period and graded according to CTCAE V5.0. Pts were followed until radiographic/clinical progression/death; LH levels were monitored every 12-weeks; normalization was defined as LH above 1.2 IU/L. PFS was defined as the time (weeks) from study enrollment and GnRH analogue discontinuation until progression or death, while OS was defined as the time to death (weeks) from any cause. We used Kaplan-Meier analysis to evaluate survival outcomes and Cox regression for multivariable modeling. Results: Between November 2018 and September 2019, 31 pts were enrolled to the study; we previously reported demographics. Median PFS was 119 weeks (95% CI: 87.1-182.1); median OS was not reached (95% CI: 163-NR); median follow up was 229 weeks. In multivariable subgroup analysis, ECOG PS of 2 compared to less than 2 was associated with shorter OS (HR: 17.8, p<0.05). The median time-to-LH normalization was 21 weeks (95% CI 15-27). Most common AEs included fatigue (n=4) hot flashes (n=5) and hypokalemia (n=2); all AEs were grade 1 except grade 3 fatigue (n=1), grade 2 hyperglycemia, (n=1) gr 2 prostatic obstruction (n=1). No treatment discontinuation due to AEs was observed. Conclusions: AAP used alone following GnRH discontinuation in pts with mPC successfully suppressed T and produced encouraging survival outcomes with an acceptable safety profile. Clinical trial information: NCT03565835 .