Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer.
BACKGROUND
Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC.


METHODS
Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate.


RESULTS
There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82-1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70-1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both).


CONCLUSIONS
Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity.


BACKGROUND
NCT01381874.
Texas Oncology-Baylor Charles A. Sammons Cancer Center/US Oncology, Dallas, USA Joyce.OShaughnessy@usoncology.com.
J
J
O'Shaughnessy
Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes.
M
M
Campone
Departments of Clinical Research and Medical Oncology, Hôpital René Huguenin, Saint-Cloud, France.
E
E
Brain
Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.
P
P
Neven
Breast Oncology Program, The University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
D
D
Hayes
Oncology Department, Municipal Clinical Hospital #4, State Medical Academy, Dnepropetrovsk, Ukraine.
I
I
Bondarenko
Janssen Research & Development, Los Angeles, USA.
T W
TW
Griffin
Janssen Research & Development, High Wycombe, UK.
J
J
Martin
Janssen Research & Development, Beerse, Belgium.
P
P
De Porre
Janssen Research & Development, Los Angeles, USA.
T
T
Kheoh
Janssen Research & Development, Los Angeles, USA.
M K
MK
Yu
Janssen Research & Development, Los Angeles, USA.
W
W
Peng
Department of Medicine, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
S
S
Johnston
D000069501:Abiraterone Acetate / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism; D016896:Treatment Outcome
D000730:Androstadienes; D011960:Receptors, Estrogen; D000069501:Abiraterone Acetate; C056516:exemestane
abiraterone acetate; androgen receptor; estrogen receptor-positive breast cancer; metastatic breast cancer; postmenopausal breast cancer