Meeting
2014 ASCO Annual Meeting
Randomized phase 2 study of abiraterone acetate (AA) with or without exemestane (E) in postmenopausal patients (pts) with estrogen receptor–positive (ER+) metastatic breast cancer (MBC).
Authors
Joyce O'Shaughnessy
Texas Oncology-Baylor Charles A. Sammons Cancer Center and US Oncology, Dallas, TX
Joyce O'Shaughnessy , Mario Campone , Etienne Brain , Patrick Neven , Daniel F. Hayes , Igor Bondarenko , Thomas W. Griffin , Jason L. Martin , Peter De Porre , Thian San Kheoh , Margaret K. Yu , Weimin Peng , Stephen R. D. Johnston
Organizations
Texas Oncology-Baylor Charles A. Sammons Cancer Center and US Oncology, Dallas, TX, Institut de Cancérologie de l'Ouest, Nantes, France, Hôpital René Huguenin, Saint-Cloud, France, University Hospitals Leuven, Leuven, Belgium, The University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, State Medical Academy, Municipal Clinical Hospital #4, Dnepropetrovsk, Ukraine, Janssen Research and Development, Los Angeles, CA, Janssen Research and Development, High Wycombe, United Kingdom, Janssen Research and Development, Beerse, Belgium, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom
Research Funding
Pharmaceutical/Biotech Company
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.
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Abstract Details
Session Type
Poster Highlights Session
Session Title
Breast Cancer - HER2/ER
Track
Breast Cancer
Sub Track
ER+
Clinical Trial Registration Number
NCT01381874
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 519)
DOI
10.1200/jco.2014.32.15_suppl.519
Abstract #
519
Poster Bd #
8
Abstract Disclosures
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