Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update ana
The first analysis of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (median follow-up, 33 months) demonstrated that in adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer, anastrozole was superior to tamoxifen in terms of disease-free survival (DFS), time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC). In the current article, the results of the first efficacy update, based on a median follow-up period of 47 months, are reported along with the results of an updated safety analysis, performed 7 months after the first analysis (median duration of treatment, 36.9 months).
DFS, TTR, CLBC incidence, and safety were assessed in the same patient group as in the first analysis of the ATAC trial.
DFS estimates at 4 years remained significantly more favorable (86.9% vs. 84.5%, respectively) for patients receiving anastrozole compared with those receiving tamoxifen (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.76-0.99; P = 0.03). The benefit generated by anastrozole in terms of DFS was even greater in patients with hormone receptor-positive tumors (HR, 0.82; 95% CI, 0.70-0.96; P = 0.014). The HR for TTR also indicated a significant benefit for patients receiving anastrozole compared with those receiving tamoxifen (HR, 0.83; 95% CI, 0.71-0.96; P = 0.015), with additional benefit for patients with hormone receptor-positive tumors (HR, 0.78; 95% CI, 0.65-0.93; P = 0.007). CLBC incidence data also continued to favor anastrozole (odds ratio [OR], 0.62; 95% CI, 0.38-1.02; P = 0.062), and statistical significance was achieved in the hormone receptor-positive subgroup (OR, 0.56; 95% CI, 0.32-0.98; P = 0.042). The updated safety analysis also confirmed the findings of the first analysis, in that endometrial cancer (P = 0.007), vaginal bleeding and discharge (P < 0.001 for both), cerebrovascular events (P < 0.001), venous thromboembolic events (P < 0.001), and hot flashes (P < 0.001) all occurred less frequently in the anastrozole group, whereas musculoskeletal disorders and fractures (P < 0.001 for both) continued to occur less frequently in the tamoxifen group. These results indicated that the safety profile of anastrozole remained consistent.
After an additional follow-up period, anastrozole continues to show superior efficacy, which is most apparent in the clinically relevant hormone receptor-positive population. Furthermore, anastrozole has numerous noteworthy advantages in terms of tolerability compared with tamoxifen. These findings suggest that the benefits of anastrozole are likely to be maintained in the long term and provide further support for the status of anastrozole as a valid treatment option for postmenopausal women with hormone-sensitive early-stage breast cancer.
Baum M
，Buzdar A
，Cuzick J
，Forbes J
，Houghton J
，Howell A
，Sahmoud T
，ATAC (Arimidex, Tamoxifen Alone or in Combination) Trialists' Group
... -
《CANCER》
Benefit and projected cost-effectiveness of anastrozole versus tamoxifen as initial adjuvant therapy for patients with early-stage estrogen receptor-positive breast cancer.
Women who have estrogen receptor (ER)-positive disease with postmenopausal onset and who receive tamoxifen as standard adjuvant treatment constitute the largest subgroup of patients with breast cancer. Recent data from the ATAC ('Arimidex, Tamoxifen Alone or in Combination') randomized trial indicate that anastrozole significantly reduces breast cancer recurrence rates but does not provide any advantage in terms of survival at 4 years posttreatment. Furthermore, anastrozole and tamoxifen were found to have different toxicity profiles. The goals of the current study were to estimate the disease-free survival (DFS) rates and potential survival benefits associated with anastrozole use and to determine whether the incremental cost-effectiveness (ICE) was low enough to warrant an immediate switch to the use of this agent, as the long-term conclusions of the ATAC trial will not be available for several years.
A computer simulation model assessed the outcomes of 64-year-old women with ER-positive breast cancer who subsequently received either anastrozole or tamoxifen for 5 years. Daily recurrence risks, as well as the relative risks associated with various treatment-related events, were calculated using data from the ATAC trial. Study endpoints included breast cancer recurrence-free survival, anticipated survival resulting from an anastrozole-induced decrease in systemic disease recurrence rates, and survival adjusted for quality of life and for hip fracture risk over periods of 4, 12, and 20 years.
After 4 years, the projected DFS benefit associated with anastrozole was 14 days, with an ICE of $167,500 per year. Projected 12 and 20 years into the future, DFS benefits increased to 2.9 months and 5.3 months, respectively. The corresponding benefits in terms of overall survival were 0.9 months and 2.0 months, respectively, with the ICE becoming < $100,000 per life year once the projection horizon exceeded 12 years. The inclusion of quality-of-life weightings for nonfatal outcomes modestly favored anastrozole in the short term; however, if anastrozole use is associated with an increased risk of hip fracture, then the long-term benefit associated with this agent is reduced by approximately 25%.
Adjuvant anastrozole is projected to result in a substantial improvement in DFS for patients with breast cancer. If this DFS benefit were to ultimately lead to a survival benefit, then the ICE of anastrozole use would be acceptable for patients expected to live longer than 12 years. Decision models are useful for generating realistic projections for stakeholders who are considering competing options that impact survival and quality of life and have associated societal costs.
Hillner BE
《CANCER》
ResearchGate
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