Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Letrozole International Trial Group (AR/BC3).
BACKGROUND
The study compares letrozole and aminoglutethimide (AG), a standard therapy for postmenopausal women with advanced breast cancer, previously treated with antioestrogens.


METHODS
555 women were randomly assigned letrozole 2.5 mg once daily (n = 185), letrozole 0.5 mg once daily (n = 192) or aminoglutethimide 250 mg twice daily with corticosteroid support (n = 178) in an open-label, multicentre trial. The primary endpoint was objective response rate (ORR), with time events as secondary. ORR was analysed nine months after enrollment of the last patient, while survival was analysed 15 months after the last patient was enrolled. We report the results of these analyses plus an extended period of observation (covering a total duration of approximately 45 months) to determine the duration of response and clinical benefit.


RESULTS
Overall objective response rates (complete + partial) of 19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg, 0.5 mg and AG respectively. Median duration of response and stable disease was longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg (18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in time to progression, time to treatment failure and overall survival. Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on AG (46%). Transient nausea was the most frequent event with letrozole (7% on 0.5 mg, 10% on 2.5 mg, 10% on AG), rash with AG (11%, 1% on 0.5 mg, 3% on 2.5 mg letrozole).


CONCLUSIONS
Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-oestrogens.
N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia.
M
M
Gershanovich
H A
HA
Chaudri
D
D
Campos
H
H
Lurie
A
A
Bonaventura
M
M
Jeffrey
F
F
Buzzi
I
I
Bodrogi
H
H
Ludwig
P
P
Reichardt
N
N
O'Higgins
G
G
Romieu
P
P
Friederich
M
M
Lassus
D000284:Administration, Oral; D000368:Aged; D000616:Aminoglutethimide / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D016017:Odds Ratio; D017698:Postmenopause; D011379:Prognosis; D015996:Survival Rate; D017211:Treatment Failure; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000616:Aminoglutethimide; D000077289:Letrozole