Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group.
OBJECTIVE
This phase III randomized open-label clinical trial was designed to evaluate the efficacy and safety of the steroidal aromatase inactivator exemestane versus the antiestrogen tamoxifen as first-line treatment for metastatic breast cancer (MBC) in postmenopausal women.


METHODS
The study was conducted at 81 centers and enrolled postmenopausal patients with measurable hormone-sensitive metastatic or locally advanced breast cancer. Prior adjuvant chemotherapy and/or tamoxifen were allowed. One previous chemotherapy regimen and no prior hormone therapy for advanced disease were permitted. Patients were randomly assigned to receive exemestane 25 mg or tamoxifen 20 mg orally once daily until disease progression or unacceptable toxicity occurred.


RESULTS
A total of 371 patients enrolled at 79 sites (182 exemestane, 189 tamoxifen) were included in the analysis. Both treatments were generally well tolerated without major toxicity. Overall response rate was greater for exemestane than for tamoxifen treatment (46% v 31%; odds ratio = 1.85; 95% CI, 1.21 to 2.82; P = .005). Median progression-free survival (PFS) was longer with exemestane (9.9 months; 95% CI, 8.7 to 11.8 months) than with tamoxifen (5.8 months; 95% CI, 5.3 to 8.1 months). However, these early differences (Wilcoxon P = .028) did not translate to a longer-term benefit in PFS, the primary study end point (log-rank P = .121). There was also no difference in survival between both study arms.


CONCLUSIONS
Exemestane is an effective and well-tolerated first-line hormonal treatment for postmenopausal women with MBC and offers significant early improvement in time to tumor progression when compared with tamoxifen.
Paridaens
Robert J
RJ
University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. robert.paridaens@uz.kuleuven.ac.be
Dirix
Luc Y
LY
Beex
Louk V
LV
Nooij
Marianne
M
Cameron
David A
DA
Cufer
Tanja
T
Piccart
Martine J
MJ
Bogaerts
Jan
J
Therasse
Patrick
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017698:Postmenopause; D012983:Soft Tissue Neoplasms / Q000556:secondary; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D013629:Tamoxifen; C056516:exemestane
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