Exemestane (Page 2 of 7)

6 ADVERSE REACTIONS

In the adjuvant treatment of early breast cancer, the most common adverse reactions occurring in ≥ 10% of patients in any treatment group (exemestane vs. tamoxifen) were mild to moderate hot flushes (21.2% vs. 19.9%), fatigue (16.1% vs. 14.7%), arthralgia (14.6% vs. 8.6%), headache (13.1% vs. 10.8%), insomnia (12.4% vs. 8.9%), and increased sweating (11.8% vs. 10.4%). Discontinuation rates due to AEs were similar between exemestane and tamoxifen (6.3% vs. 5.1%). Incidences of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) were exemestane 1.6%, tamoxifen 0.6%. Incidence of cardiac failure: exemestane 0.4%, tamoxifen 0.3%.

In the treatment of advanced breast cancer, the most common adverse reactions were mild to moderate and included hot flushes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%) for exemestane and megestrol acetate, respectively.

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adjuvant Therapy

The data described below reflect exposure to exemestane in 2,325 postmenopausal women with early breast cancer. Exemestane tolerability in postmenopausal women with early breast cancer was evaluated in two well-controlled trials: the IES study [See Clinical Studies (14.1)] and the 027 study (a randomized, placebo-controlled, double-blind, parallel group study specifically designed to assess the effects of exemestane on bone metabolism, hormones, lipids, and coagulation factors over 2 years of treatment).

The median duration of adjuvant treatment was 27.4 months and 27.3 months for patients receiving exemestane or tamoxifen, respectively, within the IES study and 23.9 months for patients receiving exemestane or placebo within the 027 study. Median duration of observation after randomization for exemestane was 34.5 months and for tamoxifen was 34.6 months. Median duration of observation was 30 months for both groups in the 027 study.

Certain adverse reactions, which were expected based on the known pharmacological properties and side effect profiles of test drugs, were actively sought through a positive checklist. Signs and symptoms were graded for severity using CTC in both studies. Within the IES study, the presence of some illnesses/conditions was monitored through a positive checklist without assessment of severity. These included myocardial infarction, other cardiovascular disorders, gynecological disorders, osteoporosis, osteoporotic fractures, other primary cancer, and hospitalizations.

Within the IES study, discontinuations due to adverse reactions occurred in 6.3% and 5.1% of patients receiving exemestane and tamoxifen, respectively, and in 12.3% and 4.1% of patients receiving exemestane or placebo respectively within study 027.

Deaths due to any cause were reported for 1.3% of the exemestane treated patients and 1.4% of the tamoxifen treated patients within the IES study. There were 6 deaths due to stroke on the exemestane arm compared to 2 on tamoxifen. There were 5 deaths due to cardiac failure on the exemestane arm compared to 2 on tamoxifen.

The incidence of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) was 1.6% in exemestane treated patients and 0.6% in tamoxifen treated patients in the IES study. Cardiac failure was observed in 0.4% of exemestane treated patients and 0.3% of tamoxifen treated patients.

Treatment-emergent adverse reactions and illnesses including all causalities and occurring with an incidence of ≥ 5% in either treatment group of the IES study during or within one month of the end of treatment are shown in Table 2.

Table . Incidence (%) of Adverse Reactions of All Grades * and Illnesses Occurring in (≥ 5%) of Patients in Any Treatment Group in Study IES in Postmenopausal Women with Early Breast Cancer
*
Graded according to Common Toxicity Criteria;
75 patients received tamoxifen 30 mg daily;
Event actively sought.

% of Patients

Body System and Adverse Reaction by MedDRA Dictionary

Exemestane 25 mg Daily (N=2,252)

Tamoxifen 20 mg Daily

(N=2,280)

Eye

Visual Disturbances

5

3.8

Gastrointestinal

Nausea

8.5

8.7

General Disorders

Fatigue

16.1

14.7

Musculoskeletal

Arthralgia

14.6

8.6

Pain in Limb

9

6.4

Back Pain

8.6

7.2

Osteoarthritis

5.9

4.5

Nervous System

Headache

13.1

10.8

Dizziness

9.7

8.4

Psychiatric

Insomnia

12.4

8.9

Depression

6.2

5.6

Skin & Subcutaneous Tissue

Increased Sweating

11.8

10.4

Vascular

Hot Flushes

21.2

19.9

Hypertension

9.8

8.4

In the IES study, as compared to tamoxifen, exemestane was associated with a higher incidence of events in musculoskeletal disorders and in nervous system disorders, including the following events occurring with frequency lower than 5% (osteoporosis [4.6% vs. 2.8%], osteochondrosis and trigger finger [0.3% vs. 0 for both events], paresthesia [2.6% vs. 0.9%], carpal tunnel syndrome [2.4% vs. 0.2%], and neuropathy [0.6% vs. 0.1%]). Diarrhea was also more frequent in the exemestane group (4.2% vs. 2.2%). Clinical fractures were reported in 94 patients receiving exemestane (4.2%) and 71 patients receiving tamoxifen (3.1%). After a median duration of therapy of about 30 months and a median follow-up of about 52 months, gastric ulcer was observed at a slightly higher frequency in the exemestane group compared to tamoxifen (0.7% vs. < 0.1%). The majority of patients on exemestane with gastric ulcer received concomitant treatment with non-steroidal anti-inflammatory agents and/or had a prior history.

Tamoxifen was associated with a higher incidence of muscle cramps [3.1% vs. 1.5%], thromboembolism [2% vs. 0.9%], endometrial hyperplasia [1.7% vs. 0.6%], and uterine polyps [2.4% vs. 0.4%].

Common adverse reactions occurring in study 027 are described in Table 3.

Table . Incidence of Selected Treatment-Emergent Adverse Reactions of all CTC Grades * Occurring in ≥ 5% of Patients in Either Arm in Study 027
*
Most events were CTC grade 1 to 2

Adverse Reaction

Exemestane N=73 (% incidence)

Placebo N=73 (% incidence)

Hot Flushes

32.9

24.7

Arthralgia

28.8

28.8

Increased Sweating

17.8

20.6

Alopecia

15.1

4.1

Hypertension

15.1

6.9

Insomnia

13.7

15.1

Nausea

12.3

16.4

Fatigue

11

19.2

Abdominal Pain

11

13.7

Depression

9.6

6.9

Diarrhea

9.6

1.4

Dizziness

9.6

9.6

Dermatitis

8.2

1.4

Headache

6.9

4.1

Myalgia

5.5

4.1

Edema

5.5

6.9

Treatment of Advanced Breast Cancer

A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program. Only one death was considered possibly related to treatment with exemestane; an 80-year-old woman with known coronary artery disease had a myocardial infarction with multiple organ failure after 9 weeks on study treatment. In the clinical trials program, only 3% of the patients discontinued treatment with exemestane because of adverse reactions, mainly within the first 10 weeks of treatment; late discontinuations because of adverse reactions were uncommon (0.3%).

In the comparative study, adverse reactions were assessed for 358 patients treated with exemestane and 400 patients treated with megestrol acetate. Fewer patients receiving exemestane discontinued treatment because of adverse reactions than those treated with megestrol acetate (2% vs. 5%). Adverse reactions that were considered drug related or of indeterminate cause included hot flashes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%) for exemestane and megestrol acetate, respectively. The proportion of patients experiencing an excessive weight gain (> 10% of their baseline weight) was significantly higher with megestrol acetate than with exemestane (17% vs. 8%). Table 4. Incidence (%) of Adverse Reactions of All Grades and Causes Occurring in ≥ 5% of Advanced Breast Cancer Patients in Each Treatment Arm in the Comparative Study shows the adverse reactions of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with exemestane or megestrol acetate.

Table . Incidence (%) of Adverse Reactions of All Grades * and Causes Occurring in ≥ 5% of Advanced Breast Cancer Patients in Each Treatment Arm in the Comparative Study
*
Graded according to Common Toxicity Criteria

Body System and Adverse Reaction by WHO ART Dictionary

Exemestane

25 mg Once Daily

(N=358)

Megestrol Acetate

40 mg QID

(N=400)

Autonomic Nervous

Increased Sweating

6

9

Body as a Whole

Fatigue

22

29

Hot Flashes

13

6

Pain

13

13

Influenza-like Symptoms

6

5

Edema (Includes Edema, Peripheral Edema, Leg Edema)

7

6

Cardiovascular

Hypertension

5

6

Nervous

Depression

13

9

Insomnia

11

9

Anxiety

10

11

Dizziness

8

6

Headache

8

7

Gastrointestinal

Nausea

18

12

Vomiting

7

4

Abdominal Pain

6

11

Anorexia

6

5

Constipation

5

8

Diarrhea

4

5

Increased Appetite

3

6

Respiratory

Dyspnea

10

15

Coughing

6

7

Less frequent adverse reactions of any cause (from 2% to 5%) reported in the comparative study for patients receiving exemestane tablets 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.

Additional adverse reactions of any cause observed in the overall clinical trials program (N = 1,058) in 5% or greater of patients treated with exemestane 25 mg once daily but not in the comparative study included pain at tumor sites (8%), asthenia (6%), and fever (5%). Adverse reactions of any cause reported in 2% to 5% of all patients treated with exemestane 25 mg in the overall clinical trials program but not in the comparative study included chest pain, hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain, infection, upper respiratory tract infection, pharyngitis, rhinitis, and alopecia.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.