Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.
OBJECTIVE
To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer.


METHODS
This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months.


RESULTS
The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001).


CONCLUSIONS
This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.
Mouridsen
Henning
H
Rigshospitalet, Copenhagen, Denmark.
Gershanovich
Mikhail
M
Sun
Yan
Y
Perez-Carrion
Ramon
R
Boni
Corrado
C
Monnier
Alain
A
Apffelstaedt
Justus
J
Smith
Robert
R
Sleeboom
Harm P
HP
Jaenicke
Fritz
F
Pluzanska
Anna
A
Dank
Magdolna
M
Becquart
Dominique
D
Bapsy
Poonamalle P
PP
Salminen
Eeva
E
Snyder
Ray
R
Chaudri-Ross
Hilary
H
Lang
Raquel
R
Wyld
Peter
P
Bhatnagar
Ajay
A
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D016016:Proportional Hazards Models; D015996:Survival Rate; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole