Letrozole (Page 4 of 12)

Bone Sub-Study

[see Warnings and Precautions (5.1)].

Lipid Sub-Study

In the extended adjuvant setting, based on a median duration of follow-up of 62 months, there was no significant difference between letrozole and placebo in total cholesterol or in any lipid fraction at any time over 5 years. Use of lipid lowering drugs or dietary management of elevated lipids was allowed [see Warnings and Precautions (5.2)].

6.3 Updated Analysis, Extended Adjuvant Treatment of Early Breast Cancer, Median Treatment Duration of 60 Months

The extended adjuvant treatment trial was unblinded early [see Adverse Reactions (6.2)]. At the updated (final analysis), overall the side effects seen were consistent to those seen at a median treatment duration of 24 months.

During treatment or within 30 days of stopping treatment (median duration of treatment 60 months) a higher rate of fractures was observed for letrozole (10.4%) compared to placebo (5.8%), as also a higher rate of osteoporosis (letrozole 12.2% vs. placebo 6.4%).

Based on 62 months median duration of follow-up in the randomized letrozole arm in the Safety population the incidence of new fractures at any time after randomization was 13.3% for letrozole and 7.8% for placebo. The incidence of new osteoporosis was 14.5% for letrozole and 7.8% for placebo.

During treatment or within 30 days of stopping treatment (median duration of treatment 60 months) the incidence of cardiovascular events was 9.8% for letrozole and 7% for placebo.

Based on 62 months median duration of follow-up in the randomized letrozole arm in the Safety population the incidence of cardiovascular disease at any time after randomization was 14.4% for letrozole and 9.8% for placebo.

Lipid Sub-Study

In the extended adjuvant setting, based on a median duration of follow-up of 62 months, there was no significant difference between letrozole and placebo in total cholesterol or in any lipid fraction over 5 years. Use of lipid lowering drugs or dietary management of elevated lipids was allowed [see Warnings and Precautions (5.2)].

6.4 First-Line Treatment of Advanced Breast Cancer

A total of 455 patients were treated for a median time of exposure of 11 months. The incidence of adverse reactions was similar for letrozole and tamoxifen. The most frequently reported adverse reactions were bone pain, hot flushes, back pain, nausea, arthralgia and dyspnea. Discontinuations for adverse reactions other than progression of tumor occurred in 10/455 (2%) of patients on letrozole and in 15/455 (3%) of patients on tamoxifen.

Adverse reactions, regardless of relationship to study drug, that were reported in at least 5% of the patients treated with letrozole 2.5 mg or tamoxifen 20 mg in the first-line treatment study are shown in Table 3.

Table 3: Percentage (%) of Patients with Adverse Reactions

Adverse

Reaction

Letrozole

2.5 mg

(N = 455)

%

Tamoxifen

20 mg

(N = 455)

%

General Disorders

Fatigue

13

13

Chest Pain

8

9

Edema Peripheral

5

6

Pain NOS

5

7

Weakness

6

4

Investigations

Weight Decreased

7

5

Vascular Disorders

Hot Flushes

19

16

Hypertension

8

4

Gastrointestinal Disorders

Nausea

17

17

Constipation

10

11

Diarrhea

8

4

Vomiting

7

8

Infections/Infestations

Influenza

6

4

Urinary Tract Infection NOS

6

3

Injury, Poisoning and Procedural Complications

Post-Mastectomy Lymphedema

7

7

Metabolism and Nutrition Disorders

Anorexia

4

6

Musculoskeletal and Connective Tissue Disorders

Bone Pain

22

21

Back Pain

18

19

Arthralgia

16

15

Pain in Limb

10

8

Nervous System Disorders

Headache NOS

8

7

Psychiatric Disorders

Insomnia

7

4

Reproductive System and Breast Disorders

Breast Pain

7

7

Respiratory, Thoracic and Mediastinal Disorders

Dyspnea

18

17

Cough

13

13

Chest Wall Pain

6

6

Other less frequent (≤ 2%) adverse reactions considered consequential for both treatment groups, included peripheral thromboembolic events, cardiovascular events, and cerebrovascular events. Peripheral thromboembolic events included venous thrombosis, thrombophlebitis, portal vein thrombosis and pulmonary embolism. Cardiovascular events included angina, myocardial infarction, myocardial ischemia, and coronary heart disease. Cerebrovascular events included transient ischemic attacks, thrombotic or hemorrhagic strokes and development of hemiparesis.

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 © 2020. All Rights Reserved.