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

Abstract

A B S T R A C T PurposeThis 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. Patients and MethodsThe 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. ResultsA 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 ϭ 1.85; 95% CI, 1.21 to 2.82; P ϭ .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 ϭ .028) did not translate to a longer-term benefit in PFS, the primary study end point (log-rank P ϭ .121). There was also no difference in survival between both study arms. ConclusionExemestane 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.

Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer

“…Computer-generated randomisation methods were used in three studies, and only one study failed to report the methods used [45]. Similarly, concealment of allocation was used in three studies with only one study failing to adequately report their methods (PO25) [31].…”

“…The full network included 4 unique studies comparing tamoxifen (20 mg/day) to letrozole [31][32][33][34][35][36][37][38][39][40], anastrozole (TARGET [30,[41][42][43] and North American [29,44] studies), and exemestane [45][46][47][48][49][50][51][52]. One study comparing anastrozole to tamoxifen (40 mg/day) [53] was excluded because the dosage was incomparable to dosages of tamoxifen used in the other studies.…”

Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial

“…The HR for PFS seen in this 321 study (0·797) is similar to the improvement shown by third-generation AIs over Page 16 tamoxifen. [4][5][6][7][8] In addition to the primary endpoint results, pre-defined subgroup 323 analyses were performed. The test for heterogeneity was not statistically significant 324 across all the subgroups although it was noted that potential enhanced treatment 325 effects with fulvestrant vs anastrozole were seen in some subgroups, including 326 patients with non-visceral disease compared with visceral disease.…”

Hot Flashes: A Review of Pathophysiology and Treatment Modalities

“…More recently, however, aromatase inhibitors have become widely used for the treatment of breast cancer in postmenopausal women. Studies comparing exemestane with tamoxifen for first-line hormonal therapy of metastatic breast cancer in postmenopausal women have shown that the incidence of hot flashes of any grade was slightly lower with exemestane (35.1%) than with tamoxifen (38.1%) [9,10]. This difference between aromatase inhibitors and tamoxifen was echoed in the Breast International Group (BIG) 1-98 and the Arimidex, Tamoxifen, Alone, or in Combination trials [11,12].…”