Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial.
OBJECTIVE
In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss.


METHODS
We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety.


RESULTS
In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms.


CONCLUSIONS
This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.
Massachusetts General Hospital Cancer Center, Lawrence House, 55 Fruit St, LRH-302, Boston, MA 02114, USA. pgoss@partners.org
Paul E
PE
Goss
James N
JN
Ingle
Kathleen I
KI
Pritchard
Matthew J
MJ
Ellis
George W
GW
Sledge
G Thomas
GT
Budd
Manuela
M
Rabaglio
Rafat H
RH
Ansari
David B
DB
Johnson
Richard
R
Tozer
David P
DP
D'Souza
Haji
H
Chalchal
Silvana
S
Spadafora
Vered
V
Stearns
Edith A
EA
Perez
Pedro E R
PE
Liedke
Istvan
I
Lang
Catherine
C
Elliott
Karen A
KA
Gelmon
Judy-Anne W
JA
Chapman
Lois E
LE
Shepherd
D000368:Aged; D000077384:Anastrozole; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D049671:History, 18th Century; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010024:Osteoporosis / Q000139:chemically induced; D017698:Postmenopause; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000730:Androstadienes; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; C056516:exemestane