Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer.
BACKGROUND
The steroidal aromatase inactivator exemestane has demonstrated activity after prior failure of non-steroidal aromatase inhibitors (including third-generation inhibitors letrozole and anastrozole) in postmenopausal women with advanced breast cancer. If exemestane is used as first anti-aromatase agent, however, it is unclear whether patients can still benefit from letrozole or anastrozole after progression.


METHODS
Postmenopausal patients with advanced, hormone receptor-positive or -unknown breast cancer were eligible for this study. Patients with no prior exposure to anti-aromatase drugs received exemestane, 25 mg daily, as first anti-aromatase agent. At the time of progression, patients were crossed-over to anastrozole or letrozole if further endocrine therapy was considered appropriate. Patients with prior exposure to anti-aromatase agents were also included in the study, and were given anastrozole or letrozole if they had previously received exemestane, or exemestane if they had previously received anastrozole or letrozole. The primary endpoint of the study was the clinical benefit rate (complete response + partial response + stabilization of disease for >or=24 weeks).


RESULTS
Forty patients received exemestane 25 mg daily as first anti-aromatase agent, with a CB rate of 67.5% (95% CI 52.9-82.0%) and a median time to progression (TTP) of 9.6 months. In 18 patients, letrozole (n = 17) or anastrozole (n = 1) were used after failure of exemestane: the CB rate was 55.6% (95% CI 32.6-78.5%) with a median TTP of 9.3 months. In 23 patients, exemestane was used after failure of letrozole or anastrozole: the CB rate was 43.5% (95% CI 23.2-63.7%) with a median TTP of 5.1 months.


CONCLUSIONS
Our study confirms that exemestane is active after prior failure of letrozole or anastrozole. We have also shown that patients can receive exemestane as their first anti-aromatase agent and still benefit from letrozole or anastrozole after progression. This suggests that the partial non-cross resistance between steroidal and non-steroidal anti-aromatase agents is independent of the sequence employed.
Bertelli
Gianfilippo
G
South West Wales Cancer Institute, Swansea, United Kingdom. gianfilippo.bertellli@swansea-tr.wales.nhs.uk
Garrone
Ornella
O
Merlano
Marco
M
Occelli
Marcella
M
Bertolotti
Laura
L
Castiglione
Federico
F
Pepi
Fiorella
F
Fusco
Ornella
O
Del Mastro
Lucia
L
Leonard
Robert C F
RC
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016001:Confidence Intervals; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
D000730:Androstadienes; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane