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Clin Cancer Res. 2016 Dec 15;22(24):6002-6009. Epub 2016 Jun 7.

Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

Author information

1
Janssen Research & Development, Spring House, Pennsylvania. wli78@its.jnj.com.
2
US Oncology, Dallas, Texas.
3
The University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
4
Institut de Cancérologie de l'Ouest, Nantes, France.
5
Dnepropetrovsk Medical Academy, Municipal Clinical Hospital #4, Dnepropetrovsk, Ukraine.
6
Leningrad Regional Oncology Dispensary, Saint Petersburg, Russia.
7
Hôpital René Huguenin, Saint-Cloud, France.
8
N.N. Blokhin Cancer Research Center, Moscow, Russia.
9
Research Institute of Oncology, Saint Petersburg, Russia.
10
CHC, Liège, Belgium.
11
University Hospitals Leuven, Leuven, Belgium.
12
Janssen Research & Development, Raritan, New Jersey.
13
Janssen Research & Development, Los Angeles, California.
14
Janssen Research & Development, San Diego, California.
15
Janssen Research & Development, Spring House, Pennsylvania.
16
Janssen Research & Development, High Wycombe, United Kingdom.
17
Janssen Research & Development, Beerse, Belgium.
18
The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom.

Abstract

PURPOSE:

Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER)+ breast cancer patients to identify subgroups with differential abiraterone sensitivity.

METHODS:

Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with ≥3 baseline CTCs (n = 104). Biomarker [e.g., androgen receptor (AR), ER, Ki-67, CYP17] expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS).

RESULTS:

Serum testosterone and estrogen levels were lowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane, but dual positivity of AR and ER expression was associated with improved PFS [HR, 0.41; 95% confidence interval (CI), 0.16-1.07; P = 0.070]. For AR expression in FFPETs obtained <1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR, 0.56; 95% CI, 0.24-1.33; P = 0.19).

CONCLUSIONS:

An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity. Clin Cancer Res; 22(24); 6002-9. ©2016 AACR.

PMID:
27267854
DOI:
10.1158/1078-0432.CCR-15-2452
[Indexed for MEDLINE]
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