The evidence supporting this protocol is provided by a phase III, multicentre, international, randomised trial (IES) involving 4724 patients comparing exemestane after two to three years of tamoxifen therapy with continuing tamoxifen therapy in postmenopausal women with primary breast cancer.r
Between 1998 and 2003, 2352 patients were randomised to receive exemestane 25 mg daily and 2372 patients were randomised to receive tamoxifen 20 mg (or 30 mg in Denmark) daily to complete a total of five years of adjuvant endocrine treatment.r
The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS), the incidence of contralateral breast cancer, and long-term tolerability.r
A review by van Hellemond et al suggests considering extended adjuvant endocrine therapy with aromatase inhibitors for a total of 5 to 10 years treatment only in women with high-risk early breast cancer who tolerate treatment well.r
Efficacy
After a median follow-up of 55.7 months, in the intention to treat group, the unadjusted hazard ratio (HR) for DFS was 0.76 (95% CI 0.66 to 0.88; p = 0.0001) in favour of exemestane. This translated into a 3.3 % (95% CI 1.6 to 4.9) absolute improvement in DFS at 2.5 years after randomisation and a 3.4% (95% CI 0.1 to 6.8) improvement 5 years after randomisation.
222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted HR 0.85 (95% CI 0.71 to 1.02, p = 0.08). When 122 patients with oestrogen-receptor- negative disease were excluded, the unadjusted HR was 0.83 (0.69 to 1.00, p = 0.05).r
Kaplan-Meier plots for disease-free survival (DFS)r
© Lancet 2007
Kaplan-Meier plots for overall survival (OS)r
© Lancet 2007
Toxicity
Patients who received exemestane reported fewer venous thromboembolic events on treatment than did those on tamoxifen. The incidence of cardiovascular events (excluding venous thromboembolic events) did not seem to differ between the groups. Musculoskeletal pain, carpel tunnel syndrome, joint stiffness, paraesthesia, and arthralgia were reported more frequently and cramp less frequently in patients who switched to exemestane than those who remained on tamoxifen. Rates of fracture per 1000 women-years were 19.2 (99% CI 15.9 to 23.1) for exemestane and 15.1 (95% CI 12.2 to 18.7) for tamoxifen.
Fewer clinically serious gynaecological events were reported in patients who switched to exemestane but the number of endometrial cancers did not differ significantly.
Adverse eventsr
© Lancet 2007
Cardiovascular, cerebrovascular and thromboembolic events for aromatase inhibitors compared to tamoxifenr
© Cancer Treat Rev 2008