Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial.
OBJECTIVE
To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial.


METHODS
This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295).


RESULTS
Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs.


CONCLUSIONS
Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy.
Crivellari
Diana
D
IBCSG Coordinating Center, Effingerstrasse 40, CH-3008 Bern, Switzerland. dcrivellari@cro.it
Sun
Zhuoxin
Z
Coates
Alan S
AS
Price
Karen N
KN
Thürlimann
Beat
B
Mouridsen
Henning
H
Mauriac
Louis
L
Forbes
John F
JF
Paridaens
Robert J
RJ
Castiglione-Gertsch
Monica
M
Gelber
Richard D
RD
Colleoni
Marco
M
Láng
István
I
Del Mastro
Lucia
L
Gladieff
Laurence
L
Rabaglio
Manuela
M
Smith
Ian E
IE
Chirgwin
Jacquie H
JH
Goldhirsch
Aron
A
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D017698:Postmenopause; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole