Letrozole in Preventing Cancer in Postmenopausal Women Who Have Received 4-6 Years of Hormone Therapy for Hormone Receptor-Positive, Lymph Node-Positive, Early-Stage Breast Cancer (SOLE)

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ClinicalTrials.gov Identifier: NCT00553410

Recruitment Status : Completed

First Posted : November 4, 2007

Results First Posted : January 29, 2019

Last Update Posted : March 11, 2020

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Sponsor:

Collaborator:

Breast International Group

Information provided by (Responsible Party):

ETOP IBCSG Partners Foundation

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition	Breast Cancer
Intervention	Drug: Letrozole
Enrollment	4884

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
Arm/Group Description	Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...
Arm/Group Description	Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
Period Title: Overall Study
Started	2441	2443
Completed	2426	2425
Not Completed	15	18

Baseline Characteristics

Arm/Group Title		Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole	Total
Arm/Group Description		Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...	Total of all reporting groups
Arm/Group Description		Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months	Total of all reporting groups
Overall Number of Baseline Participants		2426	2425	4851
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Randomized patients, regardless of eligibility status; exceptions were patients who immediately withdrew consent prior to treatment initiation and declined all participation, patients determined to be without adequate documentation of informed consent, and/or patients at a participating center determined not to be compliant with protocol procedures
Age, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	2426 participants	2425 participants	4851 participants
<55		668 27.5%	671 27.7%	1339 27.6%
55-59		504 20.8%	496 20.5%	1000 20.6%
60-64		451 18.6%	471 19.4%	922 19.0%
65-69		400 16.5%	375 15.5%	775 16.0%
70+		383 15.8%	412 17.0%	795 16.4%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2426 participants	2425 participants	4851 participants
	Female	2426 100.0%	2425 100.0%	4851 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	2426 participants	2425 participants	4851 participants
White/Caucasian		2199 90.6%	2211 91.2%	4410 90.9%
Black		10 0.4%	9 0.4%	19 0.4%
Asian		119 4.9%	121 5.0%	240 4.9%
Other		97 4.0%	83 3.4%	180 3.7%
Unknown		1 0.0%	1 0.0%	2 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	2426 participants	2425 participants	4851 participants
Hungary		78	77	155
United States		21	19	40
Japan		93	99	192
United Kingdom		217	216	433
Switzerland		159	159	318
India		8	8	16
Russia		22	21	43
Spain		137	134	271
New Zealand		10	9	19
Austria		88	92	180
Sweden		104	105	209
Belgium		509	520	1029
Denmark		223	218	441
Italy		287	291	578
South Africa		28	28	56
Australia		182	171	353
Chile		70	70	140
France		14	16	30
Peru		33	33	66
Germany		146	145	291

Outcome Measures

1.Primary Outcome


Title	Disease-free Survival (DFS)
Description	Duration of time from randomization to the first indication of the fol...
Description	Duration of time from randomization to the first indication of the following events: invasive recurrence at local (including recurrence restricted to the breast after breast conserving treatment), regional or distant sites; a new invasive cancer in the contralateral breast; any second (non-breast) invasive malignancy; or a death without prior cancer event. Appearance of DCIS or LCIS either in the ipsilateral or in the contralateral breast was not be considered as an event for DFS. In the absence of an event, DFS was censored at the date of last follow-up visit.
Time Frame	5-year estimates, reported at a median follow-up of 60 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat


Arm/Group Title	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
Arm/Group Description:	Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...
Arm/Group Description:	Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
Overall Number of Participants Analyzed	2426	2425
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of patients
	87.5 (86 to 88.8)	85.8 (84.2 to 87.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.31
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95% .93 to 1.26
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival
Description	Duration of time from randomization to death from any cause, or was ce...
Description	Duration of time from randomization to death from any cause, or was censored at the date last known alive. (Note, for patients who withdrew consent or were lost to follow-up but follow-up for survival was possible through hospital or registry records, OS was censored at the date last known alive rather than date of last follow-up/withdrawn consent).
Time Frame	5-year estimates, reported at a median follow-up of 60 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat


Arm/Group Title	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
Arm/Group Description:	Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...
Arm/Group Description:	Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
Overall Number of Participants Analyzed	2426	2425
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of patients
	93.7 (92.6 to 94.7)	94.3 (93.2 to 95.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.16
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.85
	Confidence Interval	(2-Sided) 95% .68 to 1.06
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Distant Recurrence-free Interval (DRFI)
Description	Duration of time from randomization to the first indication of invasiv...
Description	Duration of time from randomization to the first indication of invasive breast recurrence at a distant site. In the absence of an event, DRFI was censored at the date of last follow-up visit or date or death without distant recurrence.* *This endpoint replaced DDFS, which was specified in the protocol
Time Frame	5-year estimates, reported at a median follow-up of 60 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat


Arm/Group Title	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
Arm/Group Description:	Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...
Arm/Group Description:	Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
Overall Number of Participants Analyzed	2426	2425
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of patients
	92.5 (91.3 to 93.5)	93.2 (92 to 94.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.25
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.88
	Confidence Interval	(2-Sided) 95% .71 to 1.09
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Breast Cancer-free Interval
Description	Duration of time from randomization to the first indication of the fol...
Description	Duration of time from randomization to the first indication of the following events: invasive breast recurrence at local, regional or distant sites; a new invasive cancer in the contralateral breast (second non-breast malignancies are ignored). In the absence of an event, BCFI was censored at the date of last follow-up visit or date of death without prior breast cancer event.
Time Frame	5-year estimates, reported at a median follow-up of 60 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat


Arm/Group Title	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
Arm/Group Description:	Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...
Arm/Group Description:	Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
Overall Number of Participants Analyzed	2426	2425
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of patients
	91.2 (89.9 to 92.3)	90.9 (89.6 to 92.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.84
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.98
	Confidence Interval	(2-Sided) 95% .81 to 1.18
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	during or within 30 days after stopping study treatment
Adverse Event Reporting Description	Adverse event is defined as any untoward medical occurrence that occurs from the first dose of study medication until 30 days after final dose, regardless of whether it is considered related to a medication. Any known untoward event that occurs subsequent to the adverse event reporting period that the investigator assesses as possibly related to the protocol treatment should be considered an adverse event. Symptoms of the targeted cancer (if applicable) should not be reported as adverse events.

Arm/Group Title	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
Arm/Group Description	Continuous letrozole: 5 years conti...	Intermittent letrozole: 48 months o...
Arm/Group Description	Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Letrozole: Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously	Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months Letrozole: Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -> 36 mo) plus 1 x 12 mo in yr 5 -> 48 months
All-Cause Mortality
	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
	Affected / at Risk (%)	Affected / at Risk (%)
Total	170/2426 (7.01%)	146/2425 (6.02%)
Serious Adverse Events Serious Adverse Events
	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1004/2411 (41.64%)	1052/2417 (43.53%)
Blood and lymphatic system disorders
Hemoglobin ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Cardiac disorders
Cardiac Arrhythmia-Other (Specify) ^† 1	2/2411 (0.08%)	2/2417 (0.08%)
Cardiac-ischemia/infarction ^† 1	21/2411 (0.87%)	22/2417 (0.91%)
Conduction abnormality/Atrioventricular heart block - AV block-2nd degree Mobitz Type I (Wenckebach) ^† 1	0/2411 (0.00%)	2/2417 (0.08%)
Conduction abnormality/Atrioventricular heart block - AV block-third degree (complete AV block) ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Conduction abnormality/Atrioventricular heart block - Wolff-Parkinson-White syndrome ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Left ventricular diastolic dysfunction ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Left ventricular systolic dysfunction ^† 1	5/2411 (0.21%)	3/2417 (0.12%)
Pain - Cardiac/heart ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Pericardial effusion (non-malignant) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Restrictive cardiomyopathy ^† 1	1/2411 (0.04%)	2/2417 (0.08%)
Right ventricular dysfunction (cor pulmonale) ^† 1	1/2411 (0.04%)	2/2417 (0.08%)
Supraventricular and nodal arrhythmia - Atrial fibrillation ^† 1	9/2411 (0.37%)	17/2417 (0.70%)
Supraventricular and nodal arrhythmia - Atrial flutter ^† 1	3/2411 (0.12%)	0/2417 (0.00%)
Supraventricular and nodal arrhythmia - Atrial tachycardia/paroxysmal atrial tachycardia ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Supraventricular and nodal arrhythmia - Sinus bradycardia ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Supraventricular and nodal arrhythmia - Supraventricular arrhythmia NOS ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Supraventricular and nodal arrhythmia - Supraventricular tachycardia ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Valvular heart disease ^† 1	12/2411 (0.50%)	6/2417 (0.25%)
Ventricular arrhythmia - Ventricular arrhythmia NOS ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Ventricular arrhythmia - Ventricular tachycardia ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Ear and labyrinth disorders
Auditory/Ear-Other (Specify) ^† 1	3/2411 (0.12%)	8/2417 (0.33%)
Hearing: patients without baseline audiogram and not enrolled in a monitoring program ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Thyroid function, low (hypothyroidism) ^† 1	0/2411 (0.00%)	2/2417 (0.08%)
Endocrine-Other (Specify) ^† 1	3/2411 (0.12%)	2/2417 (0.08%)
Eye disorders
Cataract ^† 1	8/2411 (0.33%)	10/2417 (0.41%)
Dry eye syndrome ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Glaucoma ^† 1	0/2411 (0.00%)	2/2417 (0.08%)
Ocular/Visual-Other (Specify) ^† 1	1/2411 (0.04%)	3/2417 (0.12%)
Ophthalmoplegia/diplopia (double vision) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Retinal detachment ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Retinopathy ^† 1	0/2411 (0.00%)	2/2417 (0.08%)
Vision-blurred vision ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Vision-photophobia ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Gastrointestinal disorders
Hemorrhage, GI - Colon ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Hemorrhage, GI - Upper GI NOS ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Obstruction, GI - Cecum ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Obstruction, GI - Esophagus ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Obstruction, GI - Ileum ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Obstruction, GI - Small bowel NOS ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Ulcer, GI - Duodenum ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Colitis ^† 1	2/2411 (0.08%)	4/2417 (0.17%)
Constipation ^† 1	3/2411 (0.12%)	2/2417 (0.08%)
Dental: teeth ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Diarrhea ^† 1	5/2411 (0.21%)	5/2417 (0.21%)
Dry mouth/salivary gland (xerostomia) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Dysphagia (difficulty swallowing) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Esophagitis ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Gastritis (including bile reflux gastritis) ^† 1	2/2411 (0.08%)	2/2417 (0.08%)
Gastrointestinal-Other (Specify) ^† 1	6/2411 (0.25%)	4/2417 (0.17%)
Heartburn/dyspepsia ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Hemorrhoids ^† 1	3/2411 (0.12%)	1/2417 (0.04%)
Mucositis/stomatitis (clinical exam) - Anus ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Nausea ^† 1	1/2411 (0.04%)	2/2417 (0.08%)
Pain - Abdomen NOS ^† 1	3/2411 (0.12%)	3/2417 (0.12%)
Pain - Stomach ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Pancreatitis ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Vomiting ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
General disorders
Fatigue (asthenia, lethargy, malaise) ^† 1	58/2411 (2.41%)	48/2417 (1.99%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Constitutional Symptoms-Other (Specify) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Death not associated with CTCAE term - Death NOS ^† 1	1/2411 (0.04%)	2/2417 (0.08%)
Death not associated with CTCAE term - Sudden death ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Pain - Chest/thorax NOS ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Pain - Pain NOS ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Pain-Other (Specify) ^† 1	1/2411 (0.04%)	3/2417 (0.12%)
Hepatobiliary disorders
Obstruction, GI - Gallbladder ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Stricture/stenosis (including anastomotic), GI - Biliary tree ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Cholecystitis ^† 1	6/2411 (0.25%)	13/2417 (0.54%)
Hepatobiliary/Pancreas-Other (Specify) ^† 1	5/2411 (0.21%)	6/2417 (0.25%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever) ^† 1	5/2411 (0.21%)	1/2417 (0.04%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Brain (encephalitis, infectious) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Foreign body (e.g., graft, implant) ^† 1	3/2411 (0.12%)	3/2417 (0.12%)
Infection with unknown ANC - Foreign body (e.g., graft, implant, prosthesis, stent) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Lung (pneumonia) ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Small bowel NOS ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Kidney ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Paranasal ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Pharynx ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Abdomen NOS ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Anal/perianal ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Appendix ^† 1	4/2411 (0.17%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary) ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bone (osteomyelitis) ^† 1	0/2411 (0.00%)	3/2417 (0.12%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Brain + Spinal cord (encephalomyelitis) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bronchus ^† 1	1/2411 (0.04%)	2/2417 (0.08%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Catheter-related ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Colon ^† 1	1/2411 (0.04%)	3/2417 (0.12%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Gallbladder (cholecystitis) ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Joint ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Kidney ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia) ^† 1	6/2411 (0.25%)	8/2417 (0.33%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lymphatic ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Nerve-peripheral ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis) ^† 1	9/2411 (0.37%)	9/2417 (0.37%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Small bowel NOS ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS ^† 1	3/2411 (0.12%)	1/2417 (0.04%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Wound ^† 1	4/2411 (0.17%)	0/2417 (0.00%)
Infection with unknown ANC - Appendix ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection with unknown ANC - Dental-tooth ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Infection with unknown ANC - Larynx ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Infection with unknown ANC - Lung (pneumonia) ^† 1	7/2411 (0.29%)	3/2417 (0.12%)
Infection with unknown ANC - Skin (cellulitis) ^† 1	7/2411 (0.29%)	1/2417 (0.04%)
Infection with unknown ANC - Urinary tract NOS ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Infection with unknown ANC - Wound ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Infection-Other (Specify) ^† 1	1/2411 (0.04%)	3/2417 (0.12%)
Viral hepatitis ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Injury, poisoning and procedural complications
Wound complication, non-infectious ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Fracture ^† 1	66/2411 (2.74%)	62/2417 (2.57%)
Intra-operative injury - Joint ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Intra-operative injury - Oral ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Intra-operative injury - Spleen ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Local complication - device/prosthesis-related ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Seroma ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Thrombosis/embolism (vascular access-related) ^† 1	18/2411 (0.75%)	20/2417 (0.83%)
Vessel injury-artery - Aorta ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Vessel injury-artery - Carotid ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) ^† 1	3/2411 (0.12%)	0/2417 (0.00%)
Cholesterol, serum-high (hypercholesterolemia) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Coagulation-Other (Specify) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
GGT (gamma-glutamyl transpeptidase) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
INR (International Normalized Ratio of prothrombin time) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Lipase ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Metabolic/Laboratory-Other (Specify) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Platelets ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Weight gain ^† 1	1/2411 (0.04%)	2/2417 (0.08%)
Weight loss ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia) ^† 1	22/2411 (0.91%)	34/2417 (1.41%)
Potassium, serum-low (hypokalemia) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Sodium, serum-low (hyponatremia) ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Anorexia ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Dehydration ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Obesity ^† 1	37/2411 (1.53%)	42/2417 (1.74%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic) ^† 1	8/2411 (0.33%)	10/2417 (0.41%)
Fibrosis-deep connective tissue ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Joint-function ^† 1	8/2411 (0.33%)	12/2417 (0.50%)
Lymphedema-related fibrosis ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Musculoskeletal/Soft Tissue-Other (Specify) ^† 1	9/2411 (0.37%)	15/2417 (0.62%)
Osteonecrosis (avascular necrosis) ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Osteoporosis ^† 1	17/2411 (0.71%)	27/2417 (1.12%)
Pain - Back ^† 1	3/2411 (0.12%)	5/2417 (0.21%)
Pain - Bone ^† 1	58/2411 (2.41%)	46/2417 (1.90%)
Pain - Chest wall ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Pain - Extremity-limb ^† 1	1/2411 (0.04%)	3/2417 (0.12%)
Pain - Joint ^† 1	151/2411 (6.26%)	139/2417 (5.75%)
Pain - Muscle ^† 1	54/2411 (2.24%)	53/2417 (2.19%)
Pain - Neck ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Soft tissue necrosis - Extremity-lower ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Nervous system disorders
Hemorrhage, CNS ^† 1	7/2411 (0.29%)	9/2417 (0.37%)
Speech impairment (e.g., dysphasia or aphasia) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Ataxia (incoordination) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
CNS cerebrovascular ischemia ^† 1	31/2411 (1.29%)	24/2417 (0.99%)
Cognitive disturbance ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Dizziness ^† 1	10/2411 (0.41%)	10/2417 (0.41%)
Encephalopathy ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Memory impairment ^† 1	1/2411 (0.04%)	3/2417 (0.12%)
Mental status ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Myelitis ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Neurology-Other (Specify) ^† 1	12/2411 (0.50%)	13/2417 (0.54%)
Neuropathy: cranial - CN VII Motor-face; Sensory-taste ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Neuropathy: cranial - CN VIII Hearing and balance ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Neuropathy: motor ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Neuropathy: sensory ^† 1	3/2411 (0.12%)	2/2417 (0.08%)
Pain - Head/headache ^† 1	12/2411 (0.50%)	5/2417 (0.21%)
Pain - Neuralgia/peripheral nerve ^† 1	2/2411 (0.08%)	7/2417 (0.29%)
Seizure ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Syncope (fainting) ^† 1	5/2411 (0.21%)	9/2417 (0.37%)
Vasovagal episode ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Psychiatric disorders
Confusion ^† 1	4/2411 (0.17%)	1/2417 (0.04%)
Insomnia ^† 1	59/2411 (2.45%)	52/2417 (2.15%)
Mood alteration - anxiety ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Mood alteration - depression ^† 1	54/2411 (2.24%)	61/2417 (2.52%)
Psychosis (hallucinations/delusions) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Incontinence, urinary ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Obstruction, GU - Ureter ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Obstruction, GU - Urethra ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Cystitis ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Renal failure ^† 1	5/2411 (0.21%)	5/2417 (0.21%)
Renal/Genitourinary-Other (Specify) ^† 1	10/2411 (0.41%)	12/2417 (0.50%)
Reproductive system and breast disorders
Hemorrhage, GU - Vagina ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Pain - Pelvis ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Sexual/Reproductive Function-Other (Specify) ^† 1	3/2411 (0.12%)	4/2417 (0.17%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Lung ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Adult respiratory distress syndrome (ARDS) ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Apnea ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Aspiration ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Cough ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Dyspnea (shortness of breath) ^† 1	4/2411 (0.17%)	5/2417 (0.21%)
Hypoxia ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Obstruction/stenosis of airway - Bronchus ^† 1	3/2411 (0.12%)	2/2417 (0.08%)
Pleural effusion (non-malignant) ^† 1	1/2411 (0.04%)	0/2417 (0.00%)
Pneumonitis/pulmonary infiltrates ^† 1	2/2411 (0.08%)	1/2417 (0.04%)
Pulmonary/Upper Respiratory-Other (Specify) ^† 1	5/2411 (0.21%)	7/2417 (0.29%)
Skin and subcutaneous tissue disorders
Urticaria (hives, welts, wheals) ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Dermatology/Skin-Other (Specify) ^† 1	3/2411 (0.12%)	3/2417 (0.12%)
Nail changes ^† 1	1/2411 (0.04%)	1/2417 (0.04%)
Pruritus/itching ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Rash/desquamation ^† 1	3/2411 (0.12%)	0/2417 (0.00%)
Vascular disorders
Hematoma ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Hemorrhage/Bleeding-Other (Specify) ^† 1	0/2411 (0.00%)	3/2417 (0.12%)
Hot flashes/flushes ^† 1	70/2411 (2.90%)	59/2417 (2.44%)
Hypertension ^† 1	517/2411 (21.44%)	584/2417 (24.16%)
Hypotension ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
Peripheral arterial ischemia ^† 1	2/2411 (0.08%)	0/2417 (0.00%)
Vascular-Other (Specify) ^† 1	3/2411 (0.12%)	3/2417 (0.12%)
Vasculitis ^† 1	0/2411 (0.00%)	1/2417 (0.04%)
1 Term from vocabulary, NCI CTCAE V.3 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A: Continuous Letrozole	Arm B: Intermittent Letrozole
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2257/2411 (93.61%)	2261/2417 (93.55%)
Cardiac disorders
Cardiac-ischemia/infarction ^† 1	15/2411 (0.62%)	23/2417 (0.95%)
General disorders
Fatigue (asthenia, lethargy, malaise) ^† 1	1025/2411 (42.51%)	954/2417 (39.47%)
Injury, poisoning and procedural complications
Fracture ^† 1	148/2411 (6.14%)	136/2417 (5.63%)
Thrombosis/embolism (vascular access-related) ^† 1	8/2411 (0.33%)	9/2417 (0.37%)
Musculoskeletal and connective tissue disorders
Osteoporosis ^† 1	1113/2411 (46.16%)	1119/2417 (46.30%)
Pain - Bone ^† 1	634/2411 (26.30%)	613/2417 (25.36%)
Pain - Joint ^† 1	1506/2411 (62.46%)	1453/2417 (60.12%)
Pain - Muscle ^† 1	841/2411 (34.88%)	818/2417 (33.84%)
Nervous system disorders
Hemorrhage, CNS ^† 1	4/2411 (0.17%)	4/2417 (0.17%)
CNS cerebrovascular ischemia ^† 1	11/2411 (0.46%)	8/2417 (0.33%)
Psychiatric disorders
Insomnia ^† 1	983/2411 (40.77%)	961/2417 (39.76%)
Mood alteration - depression ^† 1	767/2411 (31.81%)	762/2417 (31.53%)
Vascular disorders
Hot flashes/flushes ^† 1	1240/2411 (51.43%)	1217/2417 (50.35%)
Hypertension ^† 1	539/2411 (22.36%)	493/2417 (20.40%)
1 Term from vocabulary, NCI CTCAE V.3 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Meredith M. Regan
Organization:	International Breast Cancer Study Group (IBCSG)
Phone:	+1 617 632 3012
EMail:	mregan@jimmy.harvard.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Guerini-Rocco E, Gray KP, Fumagalli C, Reforgiato MR, Leone I, Rafaniello Raviele P, Munzone E, Kammler R, Neven P, Hitre E, Jerusalem G, Simoncini E, Gombos A, Deleu I, Karlsson P, Aebi S, Chirgwin J, Di Lauro V, Thompson A, Graas MP, Barber M, Fontaine C, Loibl S, Gavila J, Kuroi K, Muller B, O'Reilly S, Di Leo A, Goldhirsch A, Viale G, Barberis M, Regan MM, Colleoni M. Genomic Aberrations and Late Recurrence in Postmenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the SOLE Trial. Clin Cancer Res. 2021 Jan 15;27(2):504-512. doi: 10.1158/1078-0432.CCR-20-0126. Epub 2020 Oct 20.

Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Hitre E, Graas MP, Simoncini E, Kamby C, Thompson A, Loibl S, Gavila J, Kuroi K, Marth C, Muller B, O'Reilly S, Di Lauro V, Gombos A, Ruhstaller T, Burstein H, Ribi K, Bernhard J, Viale G, Maibach R, Rabaglio-Poretti M, Gelber RD, Coates AS, Di Leo A, Regan MM, Goldhirsch A; SOLE Investigators. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):127-138. doi: 10.1016/S1470-2045(17)30715-5. Epub 2017 Nov 17.

Layout table for additonal information

Responsible Party:	ETOP IBCSG Partners Foundation
ClinicalTrials.gov Identifier:	NCT00553410
Other Study ID Numbers:	IBCSG 35-07 / BIG 1-07 2007-001370-88 ( EudraCT Number ) CDR0000574249 ( Registry Identifier: CT.gov )
First Submitted:	November 2, 2007
First Posted:	November 4, 2007
Results First Submitted:	January 4, 2019
Results First Posted:	January 29, 2019
Last Update Posted:	March 11, 2020

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