Lopez‐Gitlitz, Angela

Purpose. This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated. Results. In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23–1.36, P = 0.196 ); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression ( P = 0.02 ) in the overall population. Conclusions. HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC.

320 Background: While there is no standard therapy for BCR PC following local therapy, intermittent ADT is widely used. We evaluated utility of APA alone, ADT (luteinizing hormone–releasing hormone agonist [LHRHa]) alone, or APA + LHRHa in ADT-naïve BCR PC pts. Methods: Pts with BCR PC after primary definitive local therapy and prostate-specific antigen (PSA) doubling time (PSADT) ≤ 12 mo were randomized 1:1:1 to open-label 240 mg APA daily, LHRHa alone, or APA + LHRHa for 12 mo, followed by a 12-mo observation period off therapy. Pts were stratified by PSADT (< 6 vs 6-12 mo) and age (≤ 70 vs > 70 y). Primary end point: mean change from baseline (BL) in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy-Prostate total score at 12 mo. Secondary end points included PSA nadir < 0.2 ng/mL by 7 mo, time to PSA progression (TTPpsa), and time to testosterone (T) recovery. Results: 90 pts (APA, n = 29; LHRHa, n = 30; APA + LHRHa, n = 31) were treated for median of 12 mo with similar distribution of BL characteristics across groups: 67% age ≤ 70 y; 67% PSADT < 6 mo. There was no significant difference in HRQoL in APA vs LHRHa at 12 mo, or between LHRHa vs APA + LHRHa groups. At median follow-up of 30-33 mo, TTPpsa in APA, LHRHa, and APA + LHRHa groups was 26 mo, 31 mo, and 36 mo, respectively. Compared to LHRHa alone, APA + LHRHa resulted in a trend toward improved TTPpsa (HR [95% CI] 0.56 [0.23-1.36], p = 0.196), and APA alone resulted in a trend for shorter TTPpsa (HR 1.09 [0.49-2.43], p = 0.824). PSA nadir < 0.2 ng/mL was reached in 89%, 89%, and 97% in APA, LHRHa, and APA + LHRHa pts. Median time to T recovery was similar in LHRHa and APA + LHRHa groups (23 mo vs 24 mo). Grade 3-4 adverse events (AEs) occurred in 17% of APA, 14% of LHRHa, and 29% of APA + LHRHa pts. The only grade 3-4 AE reported in > 1 pt per group was hypertension (APA, 3%; LHRHa, 0; APA + LHRHa, 13%). Conclusions: Addition of APA to LHRHa resulted in a trend for longer TTPpsa and a higher proportion of pts achieving optimal PSA nadir without significant difference in HRQoL or time to T recovery. Observed AEs were consistent with known safety profiles. Results support further evaluation of APA + LHRHa for a specified duration in BCR PC. Clinical trial information: NCT01790126.