Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) trial.
The Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0-2, M0), or potentially operable (T4b, N0-2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated.
Patients with hormone receptor-positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery.
Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy-only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent-to-treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug-related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups.
Anastrozole is an effective and well-tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. (c) 2006 American Cancer Society.
Cataliotti L
，Buzdar AU
，Noguchi S
，Bines J
，Takatsuka Y
，Petrakova K
，Dube P
，de Oliveira CT
... -
《CANCER》
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》
Anastrozole ('Arimidex') versus tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer: results of the double-blind cross-over SAKK trial 21/95--a sub-study of the TARGET (Tamoxifen or 'Arimidex' Randomized Group Efficacy and
It is desirable to identify the most effective sequence of endocrine therapies for the treatment of postmenopausal women with advanced, hormone-responsive breast cancer. In a retrospective analysis of two large, randomized, comparative Phase III trials in this patient population, the Tamoxifen or 'Arimidex' Randomized Group Efficacy and Tolerability (TARGET) trial and the North American trial, we ascertained that tumors responding to anastrozole as first-line therapy may subsequently respond to tamoxifen as second-line therapy. In a double-blind cross-over trial, the SAKK 21/95 sub-trial (including patients from the Swiss centres in the TARGET trial), we further investigated the clinical impact of anastrozole followed by tamoxifen compared with that of tamoxifen followed by anastrozole. Patients with locally advanced or metastatic breast cancer who had continued on randomized treatment until objective disease progression and were still considered suitable for endocrine therapy, could continue on blinded therapy crossing-over to the alternative treatment. They were assessed for time to progression (TTP) from treatment randomization, TTP after crossing-over treatments, time from randomization to progression after crossing-over treatments and overall survival. Median TTP from randomization for patients receiving first-line treatment with anastrozole (n = 31) and tamoxifen (n = 29) was 11.3 and 8.3 months, respectively, p = 0.75. Median TTP from treatment cross-over was 6.7 months for tamoxifen after progression on anastrozole (n = 19) and 5.7 months for anastrozole after progression on tamoxifen (n = 18), while median time from randomization to second progression was 28.2 and 19.5 months, respectively. Overall survival from randomization for the anastrozole-tamoxifen sequence and the tamoxifen-anastrozole sequence was 69.7 versus 59.3 months, respectively, p = 0.10. The relative risk of death was higher for the tamoxifen followed by anastrozole sequence (1.63; 95% confidence interval [CI] 0.89-2.98). Tamoxifen is an effective second-line therapy after anastrozole. Our data, together with the better tolerability profile of anastrozole compared with tamoxifen, support the use of anastrozole as first-line therapy for advanced breast cancer in postmenopausal women with hormone receptor-positive tumors. Treatment with tamoxifen may still be useful upon subsequent progression.
Thürlimann B
，Hess D
，Köberle D
，Senn I
，Ballabeni P
，Pagani O
，Perey L
，Aebi S
，Rochlitz C
，Goldhirsch A
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