Analysis of two poor prognosis subgroups in ACIS evaluating apalutamide + abiraterone acetate plus prednisone (APA + AAP) versus placebo (PBO) + AAP in metastatic castration-resistant prostate cancer (mCRPC)

5037 Background: In the double-blind PBO-controlled ACIS study, investigator-assessed radiographic progression-free survival (rPFS) was significantly improved with APA + AAP vs PBO + AAP in chemo-naive mCRPC, with no significant new safety signals (Rathkopf ASCO GU 2021). Among prespecified subgroups, efficacy and safety were explored in two difficult to treat subgroups: pts with visceral disease (VD; liver, lung, and/or adrenal gland metastasis) or age ≥ 75 y. Methods: Pts with mCRPC with ongoing ADT and no prior life-prolonging treatment were randomized 1:1 to APA (240 mg QD) + AA (1000 mg QD) + P (5 mg BID) or PBO + AAP. Stratified: presence or absence of VD, ECOG PS 0 or 1, geographic region. Primary end point: rPFS (randomization to radiographic progression or death); secondary end points: overall survival (OS), time to initiation of cytotoxic chemotherapy, time to chronic opioid use, time to pain progression, safety. Results: 982 pts enrolled. 14.6% had VD and 35.9% were ≥ 75 y. Median rPFS, OS, and time to pain progression favored APA + AAP vs AAP (HR < 1) in both subgroups (Table). For pts ≥ 75 y, rPFS and OS were ≥ 7 mo longer with APA + AAP. Overall, treatment-emergent adverse events (TEAEs) were similar (all > 94%) in pts with VD, ≥ 75 y, and overall safety population; hypertension was more frequent with APA + AAP vs AAP mainly in pts ≥ 75 y (31.7% vs 17.6%). Grade 3/4 TEAEs (APA + AAP vs AAP): VD, 60.8%, n = 74 vs 48.5%, n = 68; ≥ 75 y, 71.5%, n = 186 vs 68.5%, n = 165; overall, 63.3%, n = 490 vs 56.2%, n = 489. TEAEs leading to discontinuation: VD, 17.6% vs 5.9%; ≥ 75 y, 26.3% vs 20.6%; overall, 16.9% vs 12.5%. TEAEs leading to death: VD, 6.8% vs 5.9%; ≥ 75 y, 5.4% vs 13.9%; overall, 3.5% vs 7.6%. Conclusions: In this analysis of two difficult to treat subgroups, addition of APA to AAP favored rPFS and OS. Safety, while generally consistent with the overall population, showed higher hypertension rate in ≥ 75 y and TEAEs leading to discontinuation in VD. Clinical trial information: NCT02257736. [Table: see text]