Trial Outcomes & Findings for Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy (NCT NCT00754845)

Last Updated: 2023-08-25

Results Overview

It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1918 participants

Primary outcome timeframe

Unitil the end of study with a median follow up of 75 months

Results posted on

2023-08-25

Participant Flow

Participant milestones

Participant milestones
Measure	Letrozole Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Placebo Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Overall Study STARTED	959	959
Overall Study COMPLETED	959	959
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Letrozole n=959 Participants Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Placebo n=959 Participants Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally	Total n=1918 Participants Total of all reporting groups
Age, Continuous	65.6 years n=99 Participants	64.8 years n=107 Participants	65.1 years n=206 Participants
Sex: Female, Male Female	959 Participants n=99 Participants	959 Participants n=107 Participants	1918 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=99 Participants	13 Participants n=107 Participants	24 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	940 Participants n=99 Participants	939 Participants n=107 Participants	1879 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=99 Participants	7 Participants n=107 Participants	15 Participants n=206 Participants
Region of Enrollment Canada	276 Participants n=99 Participants	285 Participants n=107 Participants	561 Participants n=206 Participants
Region of Enrollment United States	683 Participants n=99 Participants	674 Participants n=107 Participants	1357 Participants n=206 Participants
ECOG Performance Status Grade 0	852 Participants n=99 Participants	856 Participants n=107 Participants	1708 Participants n=206 Participants
ECOG Performance Status Grade 1	100 Participants n=99 Participants	95 Participants n=107 Participants	195 Participants n=206 Participants
ECOG Performance Status Grade 2	7 Participants n=99 Participants	8 Participants n=107 Participants	15 Participants n=206 Participants

PRIMARY outcome

Timeframe: Unitil the end of study with a median follow up of 75 months

Population: All women randomized were included in the analysis based on treatment arm they were randomized.

Outcome measures

Outcome measures
Measure	Letrozole n=959 Participants Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Placebo n=959 Participants Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Disease-free Survival (DFS)	0.95 probability of DFS at 5 years Interval 0.93 to 0.96	0.91 probability of DFS at 5 years Interval 0.89 to 0.93

SECONDARY outcome

Timeframe: 10 years

Population: All women randomized

The annual incidence rate was estimated based on the time to the development of contralateral breast cancer, which was calculated in months from the day of randomization to the diagnosis date of contralateral breast cancer for subjects who had developed the contralateral breast cancer, to the time of death for the patient who died, or to the last day the patient was known alive for subjects without contralateral breast cancer

Outcome measures

Outcome measures
Measure	Letrozole n=959 Participants Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Placebo n=959 Participants Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Incidence of Contralateral Breast Cancer	2.1 Number of new case per 1000 person years Interval 1.0 to 3.2	4.9 Number of new case per 1000 person years Interval 3.2 to 6.7

SECONDARY outcome

Timeframe: Until the end of study with a median follow-up of 75 months

Population: All women randomized

For subjects who died, overall survival was calculated in months from the day of randomization to the date of death. Otherwise, survival was censored at the last day the patient was known to be alive. Probability of overall survival at 5 years is estimated and reported.

Outcome measures

Outcome measures
Measure	Letrozole n=959 Participants Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Placebo n=959 Participants Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Overall Survival (OS)	0.93 probability of OS at 5 years Interval 0.92 to 0.95	0.94 probability of OS at 5 years Interval 0.92 to 0.95

SECONDARY outcome

Timeframe: 8 years

Population: All randomized patients.

Difference between post baseline scores and baseline score of role function-physical scale on SF-36 Health Survey (scale range between 0 and 100 with higher score indicating better quality of life).

Outcome measures

Outcome measures
Measure	Letrozole n=959 Participants Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Placebo n=959 Participants Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey	-7.74 score on a scale Standard Error 1.09	-6.28 score on a scale Standard Error 1.08

Adverse Events

Arm I

Serious events: 15 serious events

Other events: 863 other events

Deaths: 100 deaths

Arm II

Serious events: 19 serious events

Other events: 841 other events

Deaths: 100 deaths

Serious adverse events

Serious adverse events
Measure	Arm I n=959 participants at risk Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Arm II n=954 participants at risk Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Cardiac disorders Cardiac troponin I (cTnI)	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Cardiac disorders Thrombosis/embolism	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
General disorders Fatigue	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
General disorders Constitutional Symptoms - Other	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Renal and urinary disorders Creatinine	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Renal and urinary disorders Renal failure	0.31% 3/959 • During protocol treatment of 5 years	0.21% 2/954 • During protocol treatment of 5 years
Blood and lymphatic system disorders CNS hemorrhage/bleeding	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Blood and lymphatic system disorders Melena/GI bleeding	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
Blood and lymphatic system disorders Rectal bleeding/ hematochezia	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
Hepatobiliary disorders Liver dysfunction/ failure (clinical)	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
Hepatobiliary disorders Hepatic - Other	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
Infections and infestations Infection without neutropenia	0.21% 2/959 • During protocol treatment of 5 years	0.31% 3/954 • During protocol treatment of 5 years
Infections and infestations Infection with unknown ANC	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Nervous system disorders CNS cerebrovascular ischemia	0.00% 0/959 • During protocol treatment of 5 years	0.31% 3/954 • During protocol treatment of 5 years
Nervous system disorders Neuropathy-motor	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
General disorders Sudden death	0.42% 4/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Hypoxia	0.10% 1/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Pulmonary - Other	0.00% 0/959 • During protocol treatment of 5 years	0.21% 2/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.00% 0/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Second malignacy	0.31% 3/959 • During protocol treatment of 5 years	0.31% 3/954 • During protocol treatment of 5 years
Cardiac disorders Ventricular arrhythmia (PVCs/bigeminy/trigeminy/ ventricular tachycardia)	0.10% 1/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Cardiac disorders Edema	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
Cardiac disorders Cardiac left ventricular function	0.10% 1/959 • During protocol treatment of 5 years	0.10% 1/954 • During protocol treatment of 5 years
Cardiac disorders Cardiac-ischemia/infarction	0.21% 2/959 • During protocol treatment of 5 years	0.42% 4/954 • During protocol treatment of 5 years
Cardiac disorders Supraventricular arrhythmias (SVT/atrial fibrillation/ flutter)	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years
Cardiac disorders Cardiovascular/ General - Other	0.10% 1/959 • During protocol treatment of 5 years	0.00% 0/954 • During protocol treatment of 5 years

Other adverse events

Other adverse events
Measure	Arm I n=959 participants at risk Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. letrozole: Given orally	Arm II n=954 participants at risk Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. placebo: Given orally
Cardiac disorders Edema	16.5% 158/959 • During protocol treatment of 5 years	14.3% 136/954 • During protocol treatment of 5 years
Cardiac disorders Hypertension	16.4% 157/959 • During protocol treatment of 5 years	15.2% 145/954 • During protocol treatment of 5 years
Endocrine disorders Hot flashes/ flushes	37.5% 360/959 • During protocol treatment of 5 years	37.1% 354/954 • During protocol treatment of 5 years
General disorders Fatigue	36.1% 346/959 • During protocol treatment of 5 years	37.2% 355/954 • During protocol treatment of 5 years
General disorders Sweating	18.4% 176/959 • During protocol treatment of 5 years	18.3% 175/954 • During protocol treatment of 5 years
Gastrointestinal disorders Anorexia	4.8% 46/959 • During protocol treatment of 5 years	5.5% 52/954 • During protocol treatment of 5 years
Gastrointestinal disorders Constipation	12.2% 117/959 • During protocol treatment of 5 years	14.7% 140/954 • During protocol treatment of 5 years
Gastrointestinal disorders Diarrhea	10.9% 105/959 • During protocol treatment of 5 years	8.5% 81/954 • During protocol treatment of 5 years
Gastrointestinal disorders Dyspepsia/heartburn	9.0% 86/959 • During protocol treatment of 5 years	8.3% 79/954 • During protocol treatment of 5 years
Gastrointestinal disorders Nausea	7.2% 69/959 • During protocol treatment of 5 years	8.0% 76/954 • During protocol treatment of 5 years
Infections and infestations Infection w/o neutropenia	8.4% 81/959 • During protocol treatment of 5 years	8.6% 82/954 • During protocol treatment of 5 years
Musculoskeletal and connective tissue disorders Arthritis	33.1% 317/959 • During protocol treatment of 5 years	30.2% 288/954 • During protocol treatment of 5 years
Metabolism and nutrition disorders Hypercholesterolemia	21.2% 203/959 • During protocol treatment of 5 years	19.3% 184/954 • During protocol treatment of 5 years
Metabolism and nutrition disorders Hyperglycemia	5.8% 56/959 • During protocol treatment of 5 years	6.9% 66/954 • During protocol treatment of 5 years
Nervous system disorders Anxiety	5.6% 54/959 • During protocol treatment of 5 years	5.9% 56/954 • During protocol treatment of 5 years
Nervous system disorders Dizziness	15.1% 145/959 • During protocol treatment of 5 years	14.6% 139/954 • During protocol treatment of 5 years
Nervous system disorders Insomnia	28.1% 269/959 • During protocol treatment of 5 years	25.5% 243/954 • During protocol treatment of 5 years
Nervous system disorders Depression	15.8% 152/959 • During protocol treatment of 5 years	15.7% 150/954 • During protocol treatment of 5 years
Nervous system disorders Neuropathy-sensory	11.5% 110/959 • During protocol treatment of 5 years	11.2% 107/954 • During protocol treatment of 5 years
General disorders Abdominal pain	5.3% 51/959 • During protocol treatment of 5 years	4.0% 38/954 • During protocol treatment of 5 years
General disorders Headache	15.7% 151/959 • During protocol treatment of 5 years	14.5% 138/954 • During protocol treatment of 5 years
General disorders Arthralgia	53.5% 513/959 • During protocol treatment of 5 years	49.8% 475/954 • During protocol treatment of 5 years
General disorders Myalgia	27.9% 268/959 • During protocol treatment of 5 years	25.2% 240/954 • During protocol treatment of 5 years
General disorders Bone pain	18.1% 174/959 • During protocol treatment of 5 years	13.9% 133/954 • During protocol treatment of 5 years
General disorders Pain-Other	7.6% 73/959 • During protocol treatment of 5 years	8.1% 77/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Cough	6.6% 63/959 • During protocol treatment of 5 years	7.2% 69/954 • During protocol treatment of 5 years
Respiratory, thoracic and mediastinal disorders Dyspnea	15.4% 148/959 • During protocol treatment of 5 years	17.3% 165/954 • During protocol treatment of 5 years
Skin and subcutaneous tissue disorders Alopecia	6.4% 61/959 • During protocol treatment of 5 years	6.7% 64/954 • During protocol treatment of 5 years
Reproductive system and breast disorders Vaginal dryness	10.6% 102/959 • During protocol treatment of 5 years	10.1% 96/954 • During protocol treatment of 5 years

Additional Information

Senior Biostatistician

Canadian Cancer Trials Group

Phone: 6135336430

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place