Trial Outcomes & Findings for Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer (NCT NCT00083174)

NCT ID: NCT00083174

Last Updated: 2023-08-25

Results Overview

Percentage of serious adverse events for women who choose to receive 5 years of exemestane as preventative therapy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4560 participants

Primary outcome timeframe

5 years open-label extension period

Results posted on

2023-08-25

Participant Flow

Between February 11, 2004, and March 23, 2010, 4560 women were recruited in medical clinics.

Eligibility of women was first checked before the randomization to the trial.

Participant milestones

Participant milestones
Measure	Randomization Period: Exemestane one 25 mg tablet daily in am	Randomization Period: Placebo one tablet daily in am	Open-label Extension: Exemestane one 25 mg tablet daily in am
Randomization Period STARTED	2285	2275	0
Randomization Period COMPLETED	2285	2275	0
Randomization Period NOT COMPLETED	0	0	0
Open-label Extension STARTED	0	0	2831
Open-label Extension COMPLETED	0	0	2831
Open-label Extension NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomization Period: Exemestane n=2285 Participants one 25 mg tablet daily in am	Randomization Period: Placebo n=2275 Participants one tablet daily in am	Total n=4560 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1458 Participants n=5 Participants	1481 Participants n=7 Participants	2939 Participants n=5 Participants
Age, Categorical >=65 years	827 Participants n=5 Participants	794 Participants n=7 Participants	1621 Participants n=5 Participants
Age, Continuous	63.1 years STANDARD_DEVIATION 7.2 • n=5 Participants	63.1 years STANDARD_DEVIATION 7.0 • n=7 Participants	63.1 years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	2285 Participants n=5 Participants	2275 Participants n=7 Participants	4560 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	1416 participants n=5 Participants	1408 participants n=7 Participants	2824 participants n=5 Participants
Region of Enrollment France	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Canada	643 participants n=5 Participants	642 participants n=7 Participants	1285 participants n=5 Participants
Region of Enrollment Spain	217 participants n=5 Participants	215 participants n=7 Participants	432 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years open-label extension period

Population: Postmenopausal women who were randomized to exemestane in original MAP.3 study and chose to continue to receive exemestane for up to 5 years and those randomized to placebo and decided to start 5 years of exemestane.

Percentage of serious adverse events for women who choose to receive 5 years of exemestane as preventative therapy.

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2831 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo Placebo tablet daily
Percentage of Women With Serious Adverse Events	0.0 percentage of women Interval 0.0 to 0.5	—

PRIMARY outcome

Timeframe: Over randomization period of study (median follow-up 35 months)

Population: intention to treat (ITT)

Invasive breast cancer incidence was estimated from the breast cancer-free survival (BCFS) which was calculated for all women from the day of the randomization to the earliest date of diagnosis for invasive breast cancer. Women who died from other causes were censored at the time of death. If a woman did not develop an invasive breast cancer, or died, BCFS was censored on the date of the last day the woman was known alive (LKA), which was the latest of the date of assessment. Women who had breast cancer before study entry were also censored at the time of randomization.

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2285 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=2275 Participants Placebo tablet daily
Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)	0.19 percentage of cases/follow-up person-yr Interval 0.08 to 0.3	0.55 percentage of cases/follow-up person-yr Interval 0.36 to 0.73

SECONDARY outcome

Timeframe: Over randomization period of study (median follow-up 35 months)

Population: Intent-to-treat (ITT)

It was estimated from the Total Breast Cancer-Free Survival (TBCFS), which was calculated for women who developed invasive or non-invasive (DCIS) breast cancer as the time from the date of randomization to the earliest date of diagnosis for invasive or non-invasive (DCIS) breast cancer. Women who died from other causes were censored at the time of death. Women who had breast cancer before entry were censored at the time of randomization. If a woman did not develop an invasive or non-invasive (DCIS) breast cancer, or died, TBCFS will be censored on the date of last known alive.

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2285 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=2275 Participants Placebo tablet daily
Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer	0.35 percentage of cases/follow-up person-yr Interval 0.2 to 0.5	0.77 percentage of cases/follow-up person-yr Interval 0.54 to 0.99

SECONDARY outcome

Timeframe: Over randomization period of study (median follow-up 35 months)

Population: Intent-to-treat (ITT)

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2285 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=2275 Participants Placebo tablet daily
Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events	0.07 percentage of cases/follow-up person-yr Interval 0.0 to 0.15	0.20 percentage of cases/follow-up person-yr Interval 0.08 to 0.32

SECONDARY outcome

Timeframe: Over randomization period of study (median follow-up 35 months)

Population: Women who had at least one clinical breast biopsy

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=81 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=118 Participants Placebo tablet daily
Number of Clinical Breast Biopsies	1 number of clinical breast biopsies Interval 1.0 to 3.0	1 number of clinical breast biopsies Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: During protocol treatment over randomization period of study (up to 5 years)

Population: Women who have received treatment

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2240 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=2248 Participants Placebo tablet daily
Incidence of All Clinical Fractures	149 participants	143 participants

SECONDARY outcome

Timeframe: During protocol treatment in randomization period (up to 5 years)

Population: Women who received treatment during randomization period

Events including myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes and all vascular deaths

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2240 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=2248 Participants Placebo tablet daily
Incidence of Clinically Relevant Cardiac Events	106 participants	111 participants

SECONDARY outcome

Timeframe: Over randomization period of study (median follow-up 35 months)

Population: Women who have received treatment

Other malignancies includes any other malignancy which is not in breast.

Outcome measures

Outcome measures
Measure	Open-label Extension: Exemestane n=2240 Participants one 25 mg tablet daily in am exemestane: one 25 mg tablet daily in am	Randomization Period: Placebo n=2248 Participants Placebo tablet daily
Incidences of Other Malignancies	50 participants	42 participants

Adverse Events

Randomization Period: Exemestane

Serious events: 39 serious events

Other events: 1963 other events

Deaths: 0 deaths

Randomization Period: Placebo

Serious events: 26 serious events

Other events: 1901 other events

Deaths: 0 deaths

Open-label Extension: Exemestane

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Biostatistician

Canadian Cancer Trials Group

Phone: 613-533-6430

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Randomization Period: Exemestane n=2240 participants at risk one 25 mg tablet daily in am	Randomization Period: Placebo n=2248 participants at risk one tablet daily in am	Open-label Extension: Exemestane n=2831 participants at risk one 25 mg tablet daily in am
Cardiac disorders hypertension	15.2% 341/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	15.7% 354/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Endocrine disorders hot flashes	40.2% 900/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	31.9% 718/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Endocrine disorders fatigue	23.4% 525/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	20.7% 465/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Endocrine disorders sweating	21.7% 486/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	19.3% 433/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Endocrine disorders insomnia	10.3% 230/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	8.4% 189/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Gastrointestinal disorders Diarrhea	5.3% 118/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	3.3% 75/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Gastrointestinal disorders heartburn	14.8% 332/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	12.9% 289/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Gastrointestinal disorders Nausea	6.9% 155/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	5.4% 122/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Musculoskeletal and connective tissue disorders Arthritis	11.0% 247/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	8.7% 196/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Nervous system disorders dizziness	8.4% 189/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	9.3% 209/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Nervous system disorders mood alteration or depression	10.5% 236/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	10.5% 235/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
General disorders Pain Back	13.7% 306/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	9.9% 222/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
General disorders pain extremity	6.8% 153/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	5.4% 122/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
General disorders Pain Joint	29.7% 665/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	27.0% 606/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
General disorders pain muscle	6.6% 147/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	8.5% 192/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Respiratory, thoracic and mediastinal disorders cough	10.4% 234/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	11.8% 266/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.
Reproductive system and breast disorders vaginal dryness	15.7% 352/2240 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	15.3% 343/2248 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.	— 0/0 • Participants were followed for a median of 35 months over randomization period of study for randomization period, and 5 years for open-label extension period During 5 year open-label extension, only SAE was monitored.