Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. The Exemestane Study Group.
OBJECTIVE
This phase III, double-blind, randomized, multicenter study evaluated the efficacy, pharmacodynamics, and safety of the oral aromatase inactivator exemestane (EXE) versus megestrol acetate (MA) in postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen.


METHODS
A total of 769 patients were randomized to EXE 25 mg/d (n = 366) or MA (n = 403) 40 mg four times daily. Tumor response, duration of tumor control, tumor-related signs and symptoms (TRSS), quality of life (QOL), survival, and tolerability were evaluated.


RESULTS
Overall objective response (OR) rates were higher in patients treated with EXE than in those treated with MA (15.0% v 12.4%); a similar trend was noted in patients with visceral metastases (13.5% v 10.5%). Median survival time was significantly longer with EXE (median not reached) than with MA (123.4 weeks; P =.039), as were the median duration of overall success (OR or stable disease > or = 24 weeks; 60.1 v 49.1 weeks; P =.025), time to tumor progression (20.3 v 16.6 weeks; P =.037), and time to treatment failure (16.3 v 15.7 weeks; P =.042). Compared with MA, there were similar or greater improvements in pain, TRSS, and QOL with EXE. Both drugs were well tolerated. Grade 3 or 4 weight changes were more common with MA (17.1% v 7.6%; P =.001).


CONCLUSIONS
EXE prolongs survival time, time to tumor progression, and time to treatment failure compared with MA and offers a well-tolerated treatment option for postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen.
Kaufmann
M
M
Universitätsklinik, Frankfurt, Germany.
Bajetta
E
E
Dirix
L Y
LY
Fein
L E
LE
Jones
S E
SE
Zilembo
N
N
Dugardyn
J L
JL
Nasurdi
C
C
Mennel
R G
RG
Cervek
J
J
Fowst
C
C
Polli
A
A
di Salle
E
E
Arkhipov
A
A
Piscitelli
G
G
Miller
L L
LL
Massimini
G
G
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019290:Megestrol Acetate / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D017698:Postmenopause; D011788:Quality of Life; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
D000730:Androstadienes; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C056516:exemestane; D019290:Megestrol Acetate