Randomized Phase 2 Study Of Abiraterone Acetate (Aa) With Or Without Exemestane (E) In Postmenopausal Patients (Pts) With Estrogen Receptor-Positive (Er Plus ) Metastatic Breast Cancer (Mbc).

519 Background: Androgen receptor (AR) signaling and/or incomplete inhibition of agonistic estrogen synthesis may contribute to MBC resistance to a nonsteroidal aromatase inhibitor (NSAI). Combined inhibition of the AR with AA and the ER with E may be of clinical benefit. We assessed the safety and efficacy of AA + prednisone (P) in postmenopausal pts with NSAI-pretreated ER+ MBC. Methods: 297 pts were randomized to receive 1000 mg AA + 5 mg P (AA + P) vs AA + P with 25 mg E (AA + P + E) vs 25 mg E alone (E); 293 pts were treated. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and clinical benefit rate (CBR). Results: The median age was 63 (37-87); 64% (AA + P + E), 64% (AA + P), and 65% (E) of pts had prior NSAI for MBC while 70% (AA + P + E), 66% (AA + P), and 65% (E) had prior chemotherapy. AA + P enrollment was discontinued (n = 89) after the planned interim analysis. 181 pts had measurable disease at baseline by RECIST. There was no significant difference in PFS or CBR with AA + P or AA + P + E compared with E (Table). Median OS was not reached. Increased serum progesterone concentrations were observed in both AA arms but not with E. The grade 3 or 4 toxicities associated with AA included (AA + P + E vs E) hypokalemia (5.8% vs 2.0%), hypertension (5.8% vs 2.9%), AST increase (4.8% vs 3.9%), and ALT increase (2.9% vs 2.9%). Treatment discontinuation for treatment-emergent adverse events was uncommon and only included 6 (5.9%) in E and 10 (9.6%) pts in AA + P + E. Conclusions: Adding AA to E in NSAI-pretreated MBC pts did not improve PFS or CBR. Administration of 5 mg of P adequately suppressed AA-associated mineralocorticoid excess effects. AA-induced CYP17 inhibition may not suppress steroid hormone receptor signaling in ER+ MBC potentially due to AA-induced increased progesterone synthesis. Clinical trial information: NCT01381874. Outcome E AA + P AA + P + E n = 102 n = 89 n = 106 PFS, median (months) HR (95% CI) p value 3.7 3.7 1.1 (0.82-1.60) 0.437 4.5 0.96 (0.70-1.32) 0.794 n = 63 n = 52 n = 66 CBR, n (%) RR (95% CI) p value 8 (13) 5 (10) 0.76 (0.26-2.18) 0.603 15 (23) 1.79 (0.82-3.93) 0.137 Abbreviations: HR, hazard ratio; HR < 1 favors AA + P or AA + P + E. RR, relative risk; RR > 1 favors AA + P or AA + P + E.