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SOLE: 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

Sponsor
ETOP IBCSG Partners Foundation (Other)
Overall Status
Completed
CT.gov ID
NCT00553410
Collaborator
Breast International Group (Other)
4,884
Enrollment
164
Locations
2
Arms
141.4
Duration (Months)
29.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is more effective in postmenopausal women who have received hormone therapy for early-stage breast cancer.

PURPOSE: This randomized phase III trial is comparing two different regimens of 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

OBJECTIVES:

Primary

  • Compare the disease-free survival (DFS) of postmenopausal women treated with continuous letrozole for 5 years vs intermittent letrozole over a 5-year period.

Secondary

  • Compare overall survival of patients treated with these two regimens.

  • Compare distant DFS of these patients.

  • Compare breast cancer-free interval of these patients.

  • Compare sites of first DFS failure in these patients.

  • Compare second (nonbreast) malignancies in these patients.

  • Compare deaths without prior cancer events in these patients.

  • Compare adverse events resulting from these two regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and type of prior endocrine therapy (selective estrogen receptor modulators [SERMs] alone vs aromatase inhibitors [AIs] alone vs both SERMs and AIs each for at least 1 month). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole daily for 5 years.

  • Arm II: Patients receive oral letrozole daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.

After completion of study therapy, patients are followed annually.

Study Design

Study Type:
Interventional
Actual Enrollment :
4884 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
SOLE, Study of Letrozole Extension, A Phase III Trial Evaluating the Role of Continuous Letrozole Versus Intermittent Letrozole Following 4 to 6 Years of Prior Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone-Receptor Positive, Node Positive Early Stage Breast Cancer
Study Start Date :
Aug 1, 2007
Actual Primary Completion Date :
Apr 1, 2018
Actual Study Completion Date :
May 15, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Continuous letrozole

Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily)

Drug: Letrozole
Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously
Experimental: Intermittent letrozole

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

Drug: 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

Outcome Measures

Primary Outcome Measures

  1. Disease-free Survival (DFS) [5-year estimates, reported at a median follow-up of 60 months]

    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.

Secondary Outcome Measures

  1. Overall Survival [5-year estimates, reported at a median follow-up of 60 months]

    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).

  2. Distant Recurrence-free Interval (DRFI) [5-year estimates, reported at a median follow-up of 60 months]

    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

  3. Breast Cancer-free Interval [5-year estimates, reported at a median follow-up of 60 months]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 120 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the following criteria:

  • Steroid hormone receptor-positive tumors (estrogen receptor and/or progesterone receptor), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy

  • Prior local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease

  • Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes

  • Clinically disease-free

  • Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a sequential combination of both

  • When calculating 4-6 years, neoadjuvant endocrine therapy should not be included

  • No evidence of recurrent disease or distant metastatic disease

  • No prior bilateral breast cancer

PATIENT CHARACTERISTICS:

  • Female

  • Must be postmenopausal by any of the following criteria:

  • Patients of any age who have had a bilateral oophorectomy (including radiation castration AND amenorrheic for > 3 months)

  • Patients 56 years old or older with any evidence of ovarian function must have biochemical evidence of definite postmenopausal status (defined as estradiol, luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the postmenopausal range)

  • Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range)

  • Patients who have received prior luteinizing-hormone releasing-hormone (LHRH) analogues within the last year are eligible if they have definite evidence of postmenopausal status as defined above

  • Clinically adequate hepatic function

  • No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy

  • No prior or current malignancy except adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or ipsilateral in situ breast carcinoma

  • No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up

  • No psychiatric, addictive, or any other disorder that compromises compliance with protocol requirements

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

  • More than 12 months since prior and no other concurrent endocrine SERM/AI therapy

  • Any type of prior adjuvant therapy allowed including, but not limited to, any of the following:

  • Neoadjuvant chemotherapy

  • Neoadjuvant endocrine therapy

  • Adjuvant chemotherapy

  • Trastuzumab (Herceptin®)

  • Ovarian ablation

  • Gonadotropin releasing hormone analogues

  • Lapatinib ditosylate

  • No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of bone loss), or any other investigational agent

Contacts and Locations

Locations

Site City State Country Postal Code
1 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Boston Massachusetts United States 02115
2 Faulkner Hospital Boston Massachusetts United States 02130-3400
3 Armidale Hospital Armidale New South Wales Australia 2350
4 Bankstown - Lidcombe Hospital Bankstown New South Wales Australia 2200
5 Southern Highlands Cancer Center Bowral New South Wales Australia 2576
6 Concord Repatriation General Hospital Concord New South Wales Australia 2139
7 Breast Center Gateshead New South Wales Australia 2290
8 Port Mcquarie Base Hospital Port Macquarie New South Wales Australia 2444
9 Prince of Wales Private Hospital Randwick New South Wales Australia 2031
10 Tamworth Base Hospital Tamworth New South Wales Australia 2340
11 Tweed Heads Hospital Tweed Heads New South Wales Australia 2485
12 Calvary Mater Newcastle Waratah New South Wales Australia 2310
13 North West Regional Hospital Burnie Tasmania Australia 7320
14 Royal Hobart Hospital Hobart Tasmania Australia 7000
15 Box Hill Hospital Box Hill Victoria Australia 3128
16 Peter MacCallum Cancer Centre East Melbourne Victoria Australia 3002
17 Austin Health Heidelberg Victoria Australia 3084
18 Maroondah Hospital Melbourne Victoria Australia 3135
19 Royal Perth Hospital Perth Western Australia Australia 6000
20 Landeskrankenhaus Feldkirch Feldkirch Austria A-6807
21 Medizinische Universitaet Graz Graz Austria A-8036
22 Innsbruck Universitaetsklinik Innsbruck Austria A-6020
23 Krankenhaus BHS Linz Linz Austria A-4010
24 Allgemeines Krankenhaus Linz Linz Austria A-4021
25 St. Johanns-Spital Salzburg Austria A-5020
26 Medical University of Vienna Vienna Austria 1090
27 Allgemeines Krankenhaus - Universitatskliniken Vienna Austria A-1090
28 Krankenhaus Lainz Vienna Austria A-1130
29 Hanusch-Krankenhaus Vienna Austria A-1140
30 LKH Villach Villach Austria 9500
31 Klinikum Kreuzschwestern Wels GmbH Wels Austria 4600
32 Ziekenhuis Netwerk Antwerpen Middelheim Antwerpen Belgium B-2020
33 Cliniques du Sud Luxembourg Arlon Belgium 6700
34 Imelda vzw, Ziekenhuis Bonheiden Belgium 2820
35 AZ Klina Brasschaat Belgium 2930
36 Institut Jules Bordet Brussels Belgium 1000
37 Academisch Ziekenhuis der Vrije Universiteit Brussel Brussels Belgium 1090
38 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
39 Centre Hospitalier Universitaire Brugmann Brussels Belgium B 1020
40 Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg Duffel Belgium 2570
41 Universitair Ziekenhuis Gent Ghent Belgium B-9000
42 Hopital de Jolimont Haine Saint Paul Belgium 7100
43 Virga Jesse Hospital Hasselt Belgium 3500
44 Centre Hospitalier Hutois Huy Belgium 4500
45 AZ Groeninge - Oncologisch Centrum Kortrijk Belgium 8500
46 U.Z. Gasthuisberg Leuven Belgium B-3000
47 Centre Hospitalier de l'Ardenne Libramont Belgium 6800
48 Centre Hospitalier Regional de la Citadelle Liege Belgium 4000
49 Clinique Saint-Joseph Liege Belgium B 4000
50 CHU Liege - Domaine Universitaire du Sart Tilman Liege Belgium B-4000
51 Jan Palfijn Hospital Merksem Belgium B-2170
52 AZ Damiaan Oostende Belgium 8400
53 Clinique Saint-Pierre Ottignies Belgium B-1340
54 Clinique Saint Vincent Rocourt Belgium 4000
55 AZ Nikolaas - Sint-Niklaas Sint-Niklaas Belgium 9100
56 Sint-Elisabethziekenhuis Turnhout Belgium 2300
57 Centre Hospitalier Peltzer-La Tourelle Verviers Belgium B-4800
58 Hospital Santiago Oriente Dr. Luis Tisne Brousse Penalolen Chile 2005
59 Fundacion Arturo Lopez Perez Santiago Chile 29
60 Hospital Clinico San Borja Arriaran Santiago Chile
61 Instituto Nacional Del Cancer Santiago Chile
62 IRAM - Chile Santiago Chile
63 Hospital Clinico Regional de Valdivia at University Austral de Chile Valdivia Chile
64 Hospital Carlos Van Buren Valparaiso Chile
65 Aarhus Universitetshospital - Aarhus Sygehus Aarhus C Denmark DK-8000
66 Copenhagen County Herlev University Hospital Copenhagen Denmark DK-2730
67 Centralsygehus Esbjerg Esbjerg Denmark DK-6700
68 Herning Central Hospital Herning Denmark DK-7400
69 Hillerod Hospital Hillerod Denmark 3400
70 Naestved Hospital Naestved Denmark 4700
71 Odense University Hospital Odense Denmark DK-5000
72 Bornholms Hospital Ronne Denmark 3700
73 Roskilde Amtssygehuset Roskilde Denmark 4000
74 Sonderborg Sygehus Sonderborg Denmark 6400
75 Vejle Sygehus Vejle Denmark DK-7100
76 Viborg Sygehus Viborg Denmark 8800
77 Institut Bergonie Bordeaux France 33076
78 Aalen Breast Center Aalen Germany 73430
79 Onkologische Schwerpunktpraxis Bielefeld Bielefeld Germany D-33602
80 Allgemeinen Krankenhaus Celle Kinderklinik Celle Germany 29223
81 Klinikum Deggendorf Deggendorf Germany 94469
82 Praxis Dr. Wilke - Onkologie am Klinikum Fuerth Fuerth Germany 90766
83 Vinzenzkrankenhaus Hannover gGmbH Hannover Germany 30559
84 Henriettenstiftung Krankenhaus Hannover Germany D-30171
85 Gynaekologisch-onkologische Praxis Hannover Hannover Germany D-30177
86 Frauenheilkunde u. Geburtshilfe Ilsede Germany 31241
87 Asklepios Klinik Lich Lich Germany D-35423
88 Gemeinschaftspraxis Gynaekologie & Geburtshilfe Mannheim Germany D68161
89 Klinikum Meiningen GmbH Meiningen Germany 98617
90 Klinikum Memmingen Memmingen Germany 87700
91 Klinikum Offenback GmbH Offenbach Germany D-63069
92 Deaconess Hospital Schwabisch Hall Germany D-74523
93 Johanniter Kankenhaus Stendal Stendal Germany 39576
94 SRH Zentralklinikum Suhl GmbH Suhl Germany 98527
95 Universitaetsklinikum Tuebingen Tuebingen Germany D-72076
96 National Institute of Oncology - Budapest Budapest Hungary 1122
97 Szeged University Szeged Hungary H-6720
98 Tata Memorial Hospital Mumbai India 400012
99 Centro di Riferimento Oncologico - Aviano Aviano Italy 33081
100 Ospedale degli Infermi - ASL 12 Biella Italy 13900
101 Azienda Sanitaria di Bolzano Bolzano Italy 39100
102 Spedali Civili di Brescia Brescia Italy 25123
103 A. Perrino Hospital Brindisi Italy 72100
104 Azienda Istituti Ospitalieri Cremona Italy 26100
105 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy 47014
106 European Institute of Oncology Milan Italy 20141
107 Fondazione Salvatore Maugeri Pavia Italy I-27100
108 Misericordia e Dolce Hospital Prato Italy 59100
109 Ospedale Civile Rimini Rimini Italy 47900
110 Ospedale di Circolo e Fondazione Macchi Varese Italy 21100
111 Osaka Rosai Hospital Sakai Osaka Japan 1179-3
112 Sagara Hospital Kagoshima Japan
113 Kumamoto University Faculty of Medical and Pharmaceutical Sciences Kumamoto Japan 860-8556
114 Kyoto University Hospital Kyoto Japan 606-8507
115 Niigata Cancer Center Hospital Niigata Japan 951-8566
116 Yao Municipal Hospital Osaka Japan 581-0069
117 Tokyo Metropolitan - Komagome Hospital Tokyo Japan 113-8677
118 Christchurch Hospital Christchurch New Zealand 1
119 Waikato Hospital Hamilton New Zealand 2020
120 Instituto Nacional de Enfermedades Neoplasicas Lima Peru 34
121 Russian Academy of Medical Sciences Cancer Research Center Moscow Russian Federation 115478
122 Tygerberg Hospital Kapstadt South Africa 7505
123 Sandton Oncology Medical Research Sandton South Africa 2199
124 Vall d'Hebron University Hospital Barcelona Spain 08035
125 M. D. Anderson International Espana SA Madrid Spain 28033
126 Hospital Ramon y Cajal Madrid Spain 28034
127 Hospital Universitario 12 de Octubre Madrid Spain 28041
128 Hospital Son Llatzer Palma De Mallorca Spain 07198
129 Hospital Sant Joan de Reus Reus Spain 43201
130 Hospital Universitario Virgen Macarena Sevilla Spain 41009
131 Hospital de Torrevieja Torrevieja Spain 03180
132 Instituto Valenciano De Oncologia Valencia Spain 46009
133 Hospital Clinico Universitario de Valencia Valencia Spain 46010
134 Lasarettet i Boras Boras Sweden 501 15
135 Malarsjukhuset Hospital Eskilstuna Sweden
136 Sahlgrenska University Hospital Gothenburg Sweden S-413 45
137 Lidkoping Hospital Lidkoping Sweden S-53185
138 Skaraborgs Hospital Skovde Sweden 541 85
139 Karolinska University Hospital - Huddinge Stockholm Sweden S-141 86
140 Kantonsspital Aarau Aarau Switzerland CH-5001
141 Kantonsspital Baden Baden Switzerland CH-5404
142 Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni Bellinzona Switzerland CH-6500
143 Inselspital Bern Bern Switzerland CH-3010
144 Oncocare Sonnenhof-Klinik Engeriedspital Bern Switzerland CH-3012
145 AndreasKlinik Cham Zug Cham Switzerland CH-6330
146 Kantonsspital Graubuenden Chur Switzerland CH-7000
147 Brustzentrum Thurgau at Kantonsspital Frauenfeld Frauenfeld Switzerland 8501
148 Kantonsspital Freiburg Freiburg Switzerland 1708
149 Centre Hospitalier Universitaire Vaudois Lausanne Switzerland CH-1011
150 Lago Maggiore Oncology Foundation Locarno Switzerland 6600
151 Ospedale "la Carita", Locarno Locarno Switzerland 6600
152 Ospedale Civico Lugano Switzerland CH-6903
153 Ospedale Beata Vergine Mendrisio Switzerland CH-6850
154 Kantonsspital Olten Olten Switzerland CH-4600
155 Hopital Regional de Sion-Herens-Conthey Sion Switzerland CH -1951
156 Tumor Zentrum ZeTup St. Gallen und Chur St. Gallen Switzerland CH-9006
157 Kantonsspital - St. Gallen St. Gallen Switzerland CH-9007
158 Regionalspital Thun Switzerland 3600
159 Kantonsspital Winterthur Winterthur Switzerland CH-8400
160 Breast Center Zurich Switzerland CH-8008
161 City Hospital Triemli Zurich Switzerland CH-8063
162 UniversitaetsSpital Zuerich Zurich Switzerland CH-8091
163 Borders General Hospital Melrose England United Kingdom TD6 9BS
164 Dumfries & Galloway Royal Infirmary Dumfries Scotland United Kingdom DG1 4AP

Sponsors and Collaborators

  • ETOP IBCSG Partners Foundation
  • Breast International Group

Investigators

  • Study Chair: Marco Colleoni, MD, European Institute of Oncology

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
ETOP IBCSG Partners Foundation
ClinicalTrials.gov Identifier:
NCT00553410
Other Study ID Numbers:
  • IBCSG 35-07 / BIG 1-07
  • 2007-001370-88
  • CDR0000574249
First Posted:
Nov 4, 2007
Last Update Posted:
Mar 11, 2020
Last Verified:
May 1, 2019
Keywords provided by ETOP IBCSG Partners Foundation
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
Additional relevant MeSH terms:
Breast Neoplasms
Letrozole

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Arm A: Continuous Letrozole Arm B: Intermittent Letrozole
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 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 Participants 2426 2425 4851
Age, Customized (Count of 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%
65-69
400
16.5%
375
15.5%
775
16%
70+
383
15.8%
412
17%
795
16.4%
Sex: Female, Male (Count of Participants)
Female
2426
100%
2425
100%
4851
100%
Male
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of 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%
240
4.9%
Other
97
4%
83
3.4%
180
3.7%
Unknown
1
0%
1
0%
2
0%
Region of Enrollment (participants) [Number]
Hungary
78
3.2%
77
3.2%
155
3.2%
United States
21
0.9%
19
0.8%
40
0.8%
Japan
93
3.8%
99
4.1%
192
4%
United Kingdom
217
8.9%
216
8.9%
433
8.9%
Switzerland
159
6.6%
159
6.6%
318
6.6%
India
8
0.3%
8
0.3%
16
0.3%
Russia
22
0.9%
21
0.9%
43
0.9%
Spain
137
5.6%
134
5.5%
271
5.6%
New Zealand
10
0.4%
9
0.4%
19
0.4%
Austria
88
3.6%
92
3.8%
180
3.7%
Sweden
104
4.3%
105
4.3%
209
4.3%
Belgium
509
21%
520
21.4%
1029
21.2%
Denmark
223
9.2%
218
9%
441
9.1%
Italy
287
11.8%
291
12%
578
11.9%
South Africa
28
1.2%
28
1.2%
56
1.2%
Australia
182
7.5%
171
7.1%
353
7.3%
Chile
70
2.9%
70
2.9%
140
2.9%
France
14
0.6%
16
0.7%
30
0.6%
Peru
33
1.4%
33
1.4%
66
1.4%
Germany
146
6%
145
6%
291
6%

Outcome Measures

1. Primary Outcome
Title Disease-free Survival (DFS)
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 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
Measure Participants 2426 2425
Number (95% Confidence Interval) [percentage of patients]
87.5
85.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value .31
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
.93 to 1.26
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Overall Survival
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 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
Measure Participants 2426 2425
Number (95% Confidence Interval) [percentage of patients]
93.7
94.3
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value .16
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value .85
Confidence Interval (2-Sided) 95%
.68 to 1.06
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Distant Recurrence-free Interval (DRFI)
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 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
Measure Participants 2426 2425
Number (95% Confidence Interval) [percentage of patients]
92.5
93.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value .25
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value .88
Confidence Interval (2-Sided) 95%
.71 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Breast Cancer-free Interval
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 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
Measure Participants 2426 2425
Number (95% Confidence Interval) [percentage of patients]
91.2
90.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Continuous Letrozole, Arm B: Intermittent Letrozole
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value .84
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value .98
Confidence Interval (2-Sided) 95%
.81 to 1.18
Parameter Dispersion Type:
Value:
Estimation Comments

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 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 (%) # Events Affected / at Risk (%) # Events
Total 170/2426 (7%) 146/2425 (6%)
Serious Adverse Events
Arm A: Continuous Letrozole Arm B: Intermittent Letrozole
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1004/2411 (41.6%) 1052/2417 (43.5%)
Blood and lymphatic system disorders
Hemoglobin 1/2411 (0%) 1/2417 (0%)
Cardiac disorders
Cardiac Arrhythmia-Other (Specify) 2/2411 (0.1%) 2/2417 (0.1%)
Cardiac-ischemia/infarction 21/2411 (0.9%) 22/2417 (0.9%)
Conduction abnormality/Atrioventricular heart block - AV block-2nd degree Mobitz Type I (Wenckebach) 0/2411 (0%) 2/2417 (0.1%)
Conduction abnormality/Atrioventricular heart block - AV block-third degree (complete AV block) 2/2411 (0.1%) 0/2417 (0%)
Conduction abnormality/Atrioventricular heart block - Wolff-Parkinson-White syndrome 0/2411 (0%) 1/2417 (0%)
Left ventricular diastolic dysfunction 1/2411 (0%) 0/2417 (0%)
Left ventricular systolic dysfunction 5/2411 (0.2%) 3/2417 (0.1%)
Pain - Cardiac/heart 1/2411 (0%) 0/2417 (0%)
Pericardial effusion (non-malignant) 1/2411 (0%) 0/2417 (0%)
Restrictive cardiomyopathy 1/2411 (0%) 2/2417 (0.1%)
Right ventricular dysfunction (cor pulmonale) 1/2411 (0%) 2/2417 (0.1%)
Supraventricular and nodal arrhythmia - Atrial fibrillation 9/2411 (0.4%) 17/2417 (0.7%)
Supraventricular and nodal arrhythmia - Atrial flutter 3/2411 (0.1%) 0/2417 (0%)
Supraventricular and nodal arrhythmia - Atrial tachycardia/paroxysmal atrial tachycardia 2/2411 (0.1%) 1/2417 (0%)
Supraventricular and nodal arrhythmia - Sinus bradycardia 0/2411 (0%) 1/2417 (0%)
Supraventricular and nodal arrhythmia - Supraventricular arrhythmia NOS 1/2411 (0%) 0/2417 (0%)
Supraventricular and nodal arrhythmia - Supraventricular tachycardia 1/2411 (0%) 0/2417 (0%)
Valvular heart disease 12/2411 (0.5%) 6/2417 (0.2%)
Ventricular arrhythmia - Ventricular arrhythmia NOS 1/2411 (0%) 0/2417 (0%)
Ventricular arrhythmia - Ventricular tachycardia 2/2411 (0.1%) 1/2417 (0%)
Ear and labyrinth disorders
Auditory/Ear-Other (Specify) 3/2411 (0.1%) 8/2417 (0.3%)
Hearing: patients without baseline audiogram and not enrolled in a monitoring program 0/2411 (0%) 1/2417 (0%)
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis) 0/2411 (0%) 1/2417 (0%)
Thyroid function, low (hypothyroidism) 0/2411 (0%) 2/2417 (0.1%)
Endocrine-Other (Specify) 3/2411 (0.1%) 2/2417 (0.1%)
Eye disorders
Cataract 8/2411 (0.3%) 10/2417 (0.4%)
Dry eye syndrome 1/2411 (0%) 0/2417 (0%)
Glaucoma 0/2411 (0%) 2/2417 (0.1%)
Ocular/Visual-Other (Specify) 1/2411 (0%) 3/2417 (0.1%)
Ophthalmoplegia/diplopia (double vision) 1/2411 (0%) 0/2417 (0%)
Retinal detachment 0/2411 (0%) 1/2417 (0%)
Retinopathy 0/2411 (0%) 2/2417 (0.1%)
Vision-blurred vision 1/2411 (0%) 1/2417 (0%)
Vision-photophobia 1/2411 (0%) 0/2417 (0%)
Gastrointestinal disorders
Hemorrhage, GI - Colon 0/2411 (0%) 1/2417 (0%)
Hemorrhage, GI - Upper GI NOS 0/2411 (0%) 1/2417 (0%)
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) 0/2411 (0%) 1/2417 (0%)
Obstruction, GI - Cecum 0/2411 (0%) 1/2417 (0%)
Obstruction, GI - Esophagus 1/2411 (0%) 0/2417 (0%)
Obstruction, GI - Ileum 1/2411 (0%) 0/2417 (0%)
Obstruction, GI - Small bowel NOS 1/2411 (0%) 0/2417 (0%)
Ulcer, GI - Duodenum 0/2411 (0%) 1/2417 (0%)
Colitis 2/2411 (0.1%) 4/2417 (0.2%)
Constipation 3/2411 (0.1%) 2/2417 (0.1%)
Dental: teeth 0/2411 (0%) 1/2417 (0%)
Diarrhea 5/2411 (0.2%) 5/2417 (0.2%)
Dry mouth/salivary gland (xerostomia) 1/2411 (0%) 0/2417 (0%)
Dysphagia (difficulty swallowing) 0/2411 (0%) 1/2417 (0%)
Esophagitis 2/2411 (0.1%) 0/2417 (0%)
Gastritis (including bile reflux gastritis) 2/2411 (0.1%) 2/2417 (0.1%)
Gastrointestinal-Other (Specify) 6/2411 (0.2%) 4/2417 (0.2%)
Heartburn/dyspepsia 0/2411 (0%) 1/2417 (0%)
Hemorrhoids 3/2411 (0.1%) 1/2417 (0%)
Mucositis/stomatitis (clinical exam) - Anus 0/2411 (0%) 1/2417 (0%)
Nausea 1/2411 (0%) 2/2417 (0.1%)
Pain - Abdomen NOS 3/2411 (0.1%) 3/2417 (0.1%)
Pain - Stomach 1/2411 (0%) 0/2417 (0%)
Pancreatitis 0/2411 (0%) 1/2417 (0%)
Vomiting 1/2411 (0%) 1/2417 (0%)
General disorders
Fatigue (asthenia, lethargy, malaise) 58/2411 (2.4%) 48/2417 (2%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) 0/2411 (0%) 1/2417 (0%)
Constitutional Symptoms-Other (Specify) 0/2411 (0%) 1/2417 (0%)
Death not associated with CTCAE term - Death NOS 1/2411 (0%) 2/2417 (0.1%)
Death not associated with CTCAE term - Sudden death 2/2411 (0.1%) 0/2417 (0%)
Pain - Chest/thorax NOS 2/2411 (0.1%) 1/2417 (0%)
Pain - Pain NOS 1/2411 (0%) 0/2417 (0%)
Pain-Other (Specify) 1/2411 (0%) 3/2417 (0.1%)
Hepatobiliary disorders
Obstruction, GI - Gallbladder 1/2411 (0%) 1/2417 (0%)
Stricture/stenosis (including anastomotic), GI - Biliary tree 1/2411 (0%) 0/2417 (0%)
Cholecystitis 6/2411 (0.2%) 13/2417 (0.5%)
Hepatobiliary/Pancreas-Other (Specify) 5/2411 (0.2%) 6/2417 (0.2%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever) 5/2411 (0.2%) 1/2417 (0%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile) 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Brain (encephalitis, infectious) 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Foreign body (e.g., graft, implant) 3/2411 (0.1%) 3/2417 (0.1%)
Infection with unknown ANC - Foreign body (e.g., graft, implant, prosthesis, stent) 0/2411 (0%) 1/2417 (0%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Lung (pneumonia) 1/2411 (0%) 1/2417 (0%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Small bowel NOS 1/2411 (0%) 0/2417 (0%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Kidney 0/2411 (0%) 1/2417 (0%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Paranasal 0/2411 (0%) 1/2417 (0%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Pharynx 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Abdomen NOS 0/2411 (0%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Anal/perianal 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Appendix 4/2411 (0.2%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary) 2/2411 (0.1%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bone (osteomyelitis) 0/2411 (0%) 3/2417 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Brain + Spinal cord (encephalomyelitis) 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bronchus 1/2411 (0%) 2/2417 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Catheter-related 1/2411 (0%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Colon 1/2411 (0%) 3/2417 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Gallbladder (cholecystitis) 2/2411 (0.1%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Joint 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Kidney 1/2411 (0%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia) 6/2411 (0.2%) 8/2417 (0.3%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lymphatic 0/2411 (0%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Nerve-peripheral 0/2411 (0%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus 1/2411 (0%) 0/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis) 9/2411 (0.4%) 9/2417 (0.4%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Small bowel NOS 1/2411 (0%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS 3/2411 (0.1%) 1/2417 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Wound 4/2411 (0.2%) 0/2417 (0%)
Infection with unknown ANC - Appendix 0/2411 (0%) 1/2417 (0%)
Infection with unknown ANC - Dental-tooth 1/2411 (0%) 0/2417 (0%)
Infection with unknown ANC - Larynx 0/2411 (0%) 1/2417 (0%)
Infection with unknown ANC - Lung (pneumonia) 7/2411 (0.3%) 3/2417 (0.1%)
Infection with unknown ANC - Skin (cellulitis) 7/2411 (0.3%) 1/2417 (0%)
Infection with unknown ANC - Urinary tract NOS 2/2411 (0.1%) 1/2417 (0%)
Infection with unknown ANC - Wound 1/2411 (0%) 1/2417 (0%)
Infection-Other (Specify) 1/2411 (0%) 3/2417 (0.1%)
Viral hepatitis 0/2411 (0%) 1/2417 (0%)
Injury, poisoning and procedural complications
Wound complication, non-infectious 1/2411 (0%) 0/2417 (0%)
Fracture 66/2411 (2.7%) 62/2417 (2.6%)
Intra-operative injury - Joint 0/2411 (0%) 1/2417 (0%)
Intra-operative injury - Oral 1/2411 (0%) 0/2417 (0%)
Intra-operative injury - Spleen 1/2411 (0%) 0/2417 (0%)
Local complication - device/prosthesis-related 0/2411 (0%) 1/2417 (0%)
Seroma 1/2411 (0%) 0/2417 (0%)
Thrombosis/embolism (vascular access-related) 18/2411 (0.7%) 20/2417 (0.8%)
Vessel injury-artery - Aorta 0/2411 (0%) 1/2417 (0%)
Vessel injury-artery - Carotid 1/2411 (0%) 0/2417 (0%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) 3/2411 (0.1%) 0/2417 (0%)
Cholesterol, serum-high (hypercholesterolemia) 0/2411 (0%) 1/2417 (0%)
Coagulation-Other (Specify) 0/2411 (0%) 1/2417 (0%)
GGT (gamma-glutamyl transpeptidase) 1/2411 (0%) 0/2417 (0%)
INR (International Normalized Ratio of prothrombin time) 0/2411 (0%) 1/2417 (0%)
Lipase 0/2411 (0%) 1/2417 (0%)
Metabolic/Laboratory-Other (Specify) 1/2411 (0%) 0/2417 (0%)
Platelets 2/2411 (0.1%) 0/2417 (0%)
Weight gain 1/2411 (0%) 2/2417 (0.1%)
Weight loss 1/2411 (0%) 1/2417 (0%)
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia) 22/2411 (0.9%) 34/2417 (1.4%)
Potassium, serum-low (hypokalemia) 0/2411 (0%) 1/2417 (0%)
Sodium, serum-low (hyponatremia) 2/2411 (0.1%) 1/2417 (0%)
Anorexia 1/2411 (0%) 0/2417 (0%)
Dehydration 2/2411 (0.1%) 1/2417 (0%)
Obesity 37/2411 (1.5%) 42/2417 (1.7%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic) 8/2411 (0.3%) 10/2417 (0.4%)
Fibrosis-deep connective tissue 0/2411 (0%) 1/2417 (0%)
Joint-function 8/2411 (0.3%) 12/2417 (0.5%)
Lymphedema-related fibrosis 0/2411 (0%) 1/2417 (0%)
Musculoskeletal/Soft Tissue-Other (Specify) 9/2411 (0.4%) 15/2417 (0.6%)
Osteonecrosis (avascular necrosis) 1/2411 (0%) 1/2417 (0%)
Osteoporosis 17/2411 (0.7%) 27/2417 (1.1%)
Pain - Back 3/2411 (0.1%) 5/2417 (0.2%)
Pain - Bone 58/2411 (2.4%) 46/2417 (1.9%)
Pain - Chest wall 1/2411 (0%) 1/2417 (0%)
Pain - Extremity-limb 1/2411 (0%) 3/2417 (0.1%)
Pain - Joint 151/2411 (6.3%) 139/2417 (5.8%)
Pain - Muscle 54/2411 (2.2%) 53/2417 (2.2%)
Pain - Neck 2/2411 (0.1%) 0/2417 (0%)
Soft tissue necrosis - Extremity-lower 1/2411 (0%) 0/2417 (0%)
Nervous system disorders
Hemorrhage, CNS 7/2411 (0.3%) 9/2417 (0.4%)
Speech impairment (e.g., dysphasia or aphasia) 0/2411 (0%) 1/2417 (0%)
Ataxia (incoordination) 1/2411 (0%) 0/2417 (0%)
CNS cerebrovascular ischemia 31/2411 (1.3%) 24/2417 (1%)
Cognitive disturbance 1/2411 (0%) 0/2417 (0%)
Dizziness 10/2411 (0.4%) 10/2417 (0.4%)
Encephalopathy 2/2411 (0.1%) 0/2417 (0%)
Memory impairment 1/2411 (0%) 3/2417 (0.1%)
Mental status 1/2411 (0%) 0/2417 (0%)
Myelitis 1/2411 (0%) 0/2417 (0%)
Neurology-Other (Specify) 12/2411 (0.5%) 13/2417 (0.5%)
Neuropathy: cranial - CN VII Motor-face; Sensory-taste 1/2411 (0%) 0/2417 (0%)
Neuropathy: cranial - CN VIII Hearing and balance 1/2411 (0%) 0/2417 (0%)
Neuropathy: motor 1/2411 (0%) 1/2417 (0%)
Neuropathy: sensory 3/2411 (0.1%) 2/2417 (0.1%)
Pain - Head/headache 12/2411 (0.5%) 5/2417 (0.2%)
Pain - Neuralgia/peripheral nerve 2/2411 (0.1%) 7/2417 (0.3%)
Seizure 1/2411 (0%) 0/2417 (0%)
Syncope (fainting) 5/2411 (0.2%) 9/2417 (0.4%)
Vasovagal episode 0/2411 (0%) 1/2417 (0%)
Psychiatric disorders
Confusion 4/2411 (0.2%) 1/2417 (0%)
Insomnia 59/2411 (2.4%) 52/2417 (2.2%)
Mood alteration - anxiety 2/2411 (0.1%) 0/2417 (0%)
Mood alteration - depression 54/2411 (2.2%) 61/2417 (2.5%)
Psychosis (hallucinations/delusions) 1/2411 (0%) 0/2417 (0%)
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS 1/2411 (0%) 0/2417 (0%)
Incontinence, urinary 2/2411 (0.1%) 1/2417 (0%)
Obstruction, GU - Ureter 0/2411 (0%) 1/2417 (0%)
Obstruction, GU - Urethra 1/2411 (0%) 0/2417 (0%)
Cystitis 1/2411 (0%) 1/2417 (0%)
Renal failure 5/2411 (0.2%) 5/2417 (0.2%)
Renal/Genitourinary-Other (Specify) 10/2411 (0.4%) 12/2417 (0.5%)
Reproductive system and breast disorders
Hemorrhage, GU - Vagina 1/2411 (0%) 0/2417 (0%)
Pain - Pelvis 1/2411 (0%) 0/2417 (0%)
Sexual/Reproductive Function-Other (Specify) 3/2411 (0.1%) 4/2417 (0.2%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Lung 1/2411 (0%) 0/2417 (0%)
Adult respiratory distress syndrome (ARDS) 0/2411 (0%) 1/2417 (0%)
Apnea 2/2411 (0.1%) 0/2417 (0%)
Aspiration 0/2411 (0%) 1/2417 (0%)
Cough 1/2411 (0%) 0/2417 (0%)
Dyspnea (shortness of breath) 4/2411 (0.2%) 5/2417 (0.2%)
Hypoxia 1/2411 (0%) 0/2417 (0%)
Obstruction/stenosis of airway - Bronchus 3/2411 (0.1%) 2/2417 (0.1%)
Pleural effusion (non-malignant) 1/2411 (0%) 0/2417 (0%)
Pneumonitis/pulmonary infiltrates 2/2411 (0.1%) 1/2417 (0%)
Pulmonary/Upper Respiratory-Other (Specify) 5/2411 (0.2%) 7/2417 (0.3%)
Skin and subcutaneous tissue disorders
Urticaria (hives, welts, wheals) 2/2411 (0.1%) 0/2417 (0%)
Dermatology/Skin-Other (Specify) 3/2411 (0.1%) 3/2417 (0.1%)
Nail changes 1/2411 (0%) 1/2417 (0%)
Pruritus/itching 0/2411 (0%) 1/2417 (0%)
Rash/desquamation 3/2411 (0.1%) 0/2417 (0%)
Vascular disorders
Hematoma 0/2411 (0%) 1/2417 (0%)
Hemorrhage/Bleeding-Other (Specify) 0/2411 (0%) 3/2417 (0.1%)
Hot flashes/flushes 70/2411 (2.9%) 59/2417 (2.4%)
Hypertension 517/2411 (21.4%) 584/2417 (24.2%)
Hypotension 0/2411 (0%) 1/2417 (0%)
Peripheral arterial ischemia 2/2411 (0.1%) 0/2417 (0%)
Vascular-Other (Specify) 3/2411 (0.1%) 3/2417 (0.1%)
Vasculitis 0/2411 (0%) 1/2417 (0%)
Other (Not Including Serious) Adverse Events
Arm A: Continuous Letrozole Arm B: Intermittent Letrozole
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2257/2411 (93.6%) 2261/2417 (93.5%)
Cardiac disorders
Cardiac-ischemia/infarction 15/2411 (0.6%) 23/2417 (1%)
General disorders
Fatigue (asthenia, lethargy, malaise) 1025/2411 (42.5%) 954/2417 (39.5%)
Injury, poisoning and procedural complications
Fracture 148/2411 (6.1%) 136/2417 (5.6%)
Thrombosis/embolism (vascular access-related) 8/2411 (0.3%) 9/2417 (0.4%)
Musculoskeletal and connective tissue disorders
Osteoporosis 1113/2411 (46.2%) 1119/2417 (46.3%)
Pain - Bone 634/2411 (26.3%) 613/2417 (25.4%)
Pain - Joint 1506/2411 (62.5%) 1453/2417 (60.1%)
Pain - Muscle 841/2411 (34.9%) 818/2417 (33.8%)
Nervous system disorders
Hemorrhage, CNS 4/2411 (0.2%) 4/2417 (0.2%)
CNS cerebrovascular ischemia 11/2411 (0.5%) 8/2417 (0.3%)
Psychiatric disorders
Insomnia 983/2411 (40.8%) 961/2417 (39.8%)
Mood alteration - depression 767/2411 (31.8%) 762/2417 (31.5%)
Vascular disorders
Hot flashes/flushes 1240/2411 (51.4%) 1217/2417 (50.4%)
Hypertension 539/2411 (22.4%) 493/2417 (20.4%)

Limitations/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

Name/Title Meredith M. Regan
Organization International Breast Cancer Study Group (IBCSG)
Phone +1 617 632 3012
Email mregan@jimmy.harvard.edu
Responsible Party:
ETOP IBCSG Partners Foundation
ClinicalTrials.gov Identifier:
NCT00553410
Other Study ID Numbers:
  • IBCSG 35-07 / BIG 1-07
  • 2007-001370-88
  • CDR0000574249
First Posted:
Nov 4, 2007
Last Update Posted:
Mar 11, 2020
Last Verified:
May 1, 2019