Anastrozol (anastrozole) coated tablets 1 mg. №28

active ingredient : anastrozole;

1 coated tablet contains 1 mg of anastrozole;

excipients: lactose; sodium starch, povidone, magnesium stearate

polyethylene glycol (PEG 400) *, hypromellose *, titanium dioxide (E 171) *.

* – excipients related to the film shell.

Film-coated tablets.

Basic physical and chemical properties : white, round, biconvex film-coated tablets.

Hormone antagonists and related agents. aromatase inhibitors. ATX code L02B G03.

Mechanism of action and pharmacodynamic effects

Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. In postmenopausal women, estradiol is mainly produced by the conversion of androstenedione to estrone in peripheral tissues by the aromatase enzyme complex. Estrone is further converted to estradiol. Reducing the level of estradiol has a therapeutic effect in women with breast cancer. In postmenopausal women, taking anastrozole at a daily dose of 1 mg led to an 80% decrease in estradiol levels, which was confirmed by a highly sensitive analytical test.

Anastrozole has no progestogenic, androgenic or estrogenic activity.

Anastrozole at a daily dose of up to 10 mg does not affect the secretion of cortisol and aldosterone, which was measured before and after the standard ACTH stimulation test (ACTH). Therefore, there is no need for corticosteroid replacement.

Clinical efficacy and safety

Advanced breast cancer

First line therapy for postmenopausal women with advanced breast cancer

Two similarly designed, double-blind, controlled clinical trials (study 1033IL/0030 and study 1033IL/0027) were conducted to evaluate the efficacy of anastrozole versus tamoxifen as a first-line treatment for locally advanced or metastatic breast cancer with receptor positive or unknown receptors. hormones in postmenopausal women. A total of 1021 patients were randomized to receive anastrozole 1 mg once daily or tamoxifen 20 mg once daily. The main endpoints in both studies were time to tumor progression, objective tumor response rate, and safety.

Evaluation of the main endpoints of the 1033IL/0030 study demonstrated that anastrozole had a statistically significant advantage over tamoxifen in time to tumor progression (hazard ratio (RR) 1.42; 95% confidence interval (CI) [1.11; 1.82], median time to progression of 11.1 and 5.6 months for anastrozole and tamoxifen, respectively, p = 0.006), the objective tumor response rate was similar for anastrozole and tamoxifen. The 1033IL/0027 study demonstrated that the objective tumor response rate and time to tumor progression for anastrozole and tamoxifen were similar. The assessment of the secondary endpoints confirmed the assessment of the main performance endpoints.

Second line therapy for postmenopausal women with advanced breast cancer

Anastrozole was studied in two controlled clinical trials (study 0004 and 0005) in postmenopausal women with advanced breast cancer,

in whom the disease progressed after treatment with tamoxifen for advanced breast cancer or early-stage breast cancer. A total of 764 patients were randomized to receive anastrozole 1 mg or 10 mg once daily or megestrol acetate 40 mg four times daily. Time to progression and objective response rate were primary measures of efficacy. The frequency of cases of prolonged (more than 24 weeks) stable disease, the frequency of progression and overall survival were also determined. In both studies, there were no significant differences between treatment groups in any of the efficacy parameters.

Additive treatment of invasive breast cancer with positive indicators of hormone receptors in the early stages

In a large phase III study conducted in 9366 postmenopausal women with operable breast cancer who were treated for 5 years (see below), anastrozole statistically dominated tamoxifen relative to disease-free survival. Significantly greater benefits in terms of disease-free survival have been observed in favor of anastrozole over tamoxifen in a prospectively defined hormone receptor positive population.

Table 1

Summary Table of Outcomes from the ATAS Study: Post-Treatment Analysis of 5 Years

(a) Disease-free survival includes all recurrences and is defined as the first episode of local regional recurrence, contralateral breast cancer, distant recurrence, or death (from any cause).

b – Survival without metastasis of the disease is defined as the first episode of recurrent metastasis or death (from any cause).

c – hour to recurrence is defined as the first episode of local regional recurrence, contralateral breast cancer, distant recurrence, or death due to breast cancer.

d – Hour before recurrence of metastasis is defined as the first episode of recurrence of metastasis or death due to breast cancer.

e – Kilkist (%) of patients who died.

The combination of anastrozole and tamoxifen was not superior to tamoxifen in all patients, nor in the hormone receptor positive group. This treatment group was withdrawn from the study.

Based on updated follow-up data with a median of 10 years, the long-term effects of treatment with anastrozole compared with tamoxifen are consistent with previous analyses.

Treatment additive for early-stage hormone receptor-positive invasive breast cancer in women treated with adjuvant tamoxifen

In a phase III clinical trial (Austrian Breast and Colorectal Cancer Study Group [ABCSG] 8) of 2579 postmenopausal women with early hormone receptor positive breast cancer who underwent surgery with or without radiotherapy her, but who did not receive chemotherapy (see below), disease-free survival rates in the group of patients who were switched to anastrozole after 2 years of adjuvant therapy with tamoxifen were statistically dominated by such rates in the group of patients who continued to use tamoxifen after a period of follow-up with median 24 months.

table 2

Summary Table of Outcomes and Results of ABCSG Study 8

Two further similar studies (GABG/ARNO 95 and ITA), in one of which patients received surgery and chemotherapy, and a combined analysis of the ABCSG 8 and GABG/ARNO 95 studies support these results.

The safety of anastrozole in these three studies was consistent with the safety profile established in postmenopausal women with early hormone receptor positive breast cancer.

Bone Mineral Density (BMD)

In a phase III/IV study (Study of Anastrozole with the Bisphosphonate Risedronate [SABRE]), 234 hormone receptor-positive postmenopausal women with early breast cancer who were scheduled to receive anastrozole 1 mg/day were divided into low , medium and high risk according to their risk of osteoporotic fracture. The primary efficacy parameter was lumbar spine bone density analysis using a DEXA scan. All patients received vitamin D and calcium. Patients in the low-risk group received only anastrozole (N = 42), patients in the intermediate risk group were randomized to receive anastrozole plus risedronate 35 mg once weekly (N = 77) or anastrozole plus placebo (N = 77) patients in the high risk group received anastrozole plus risedronate 35 mg 1 time per week (N = 38). The primary endpoint was change in bone density in the lumbar spine at 12 months from baseline.

The main analysis at 12 months showed that in patients with an average and high risk of osteoporotic fracture, there was no decrease in bone mass (estimated bone mineral density of the lumbar spine using a DEXA scan) when using anastrozole at a dose of 1 mg / day in combination with risedronate 35 mg once a week. In addition, a decrease in BMD, which was not statistically significant, was observed in the low-risk group when using only anastrozole at a dose of 1 mg / day. These results were reflected in an additional efficacy variable, change in total hip BMD at 12 months from baseline.

This study argues that it is reasonable to consider the use of bisphosphonates for possible bone loss in postmenopausal women with early breast cancer who are scheduled to receive anastrozole.