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Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study (Neo ALTTO)

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ClinicalTrials.gov Identifier: NCT00553358
Recruitment Status : Completed
First Posted : November 4, 2007
Results First Posted : October 13, 2011
Last Update Posted : June 3, 2021
Sponsor:
Collaborators:
Breast International Group
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms, Breast
Interventions Drug: Lapatinib
Biological: Trastuzumab
Drug: Paclitaxel
Enrollment 455
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Period Title: Overall Study
Started 152 154 149
Completed [1] 73 58 61
Not Completed 79 96 88
Reason Not Completed
Randomized but did not receive treatment             3             3             1
Lost to Follow-up             22             26             18
Withdrew completely             23             33             34
Died during clinical follow-up             25             29             32
Not dead but were last followed-up prior to 9 years + 6 months after randomization             4             2             2
Died after clinical follow-up ended             1             2             0
Withdrew (survival only) - alive at end of survival follow-up             1             1             1
[1]
Completed follow-up per protocol event free. Includes subjects who had a follow-up visit or phone call ≥ 9 years + 6 months after randomization and had no EFS events
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Total
Hide Arm/Group Description Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 154 149 152 455
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 154 participants 149 participants 152 participants 455 participants
50.0
(28 to 79)
49.0
(23 to 77)
50.0
(25 to 80)
50.0
(23 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Female
154
 100.0%
149
 100.0%
152
 100.0%
455
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
American Indian or Alaska Native
13
   8.4%
14
   9.4%
15
   9.9%
42
   9.2%
Asian - Central/South
7
   4.5%
5
   3.4%
5
   3.3%
17
   3.7%
Asian - East
30
  19.5%
28
  18.8%
31
  20.4%
89
  19.6%
Asian - South East
0
   0.0%
0
   0.0%
2
   1.3%
2
   0.4%
Black or African American/African Heritage
0
   0.0%
4
   2.7%
4
   2.6%
8
   1.8%
White - Arabic/North African Heritage
6
   3.9%
5
   3.4%
3
   2.0%
14
   3.1%
White - Caucasian European Heritage
97
  63.0%
93
  62.4%
92
  60.5%
282
  62.0%
Missing
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Number of participants with tumor cells of the indicated histologic grade   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Well differentiated
2
   1.3%
5
   3.4%
5
   3.3%
12
   2.6%
Moderately differentiated
56
  36.4%
53
  35.6%
63
  41.4%
172
  37.8%
Poorly differentiated
73
  47.4%
68
  45.6%
64
  42.1%
205
  45.1%
Differentiation cannot be assessed
22
  14.3%
23
  15.4%
20
  13.2%
65
  14.3%
Missing
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
[1]
Measure Description: Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type.
Number of participants with lymph nodes (LNs) of the indicated clinical N stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
N0
34
  22.1%
41
  27.5%
48
  31.6%
123
  27.0%
N1
95
  61.7%
85
  57.0%
80
  52.6%
260
  57.1%
N2 (including N2a and N2b)
19
  12.3%
13
   8.7%
15
   9.9%
47
  10.3%
N3 (including N3a, N3b, and N3c)
6
   3.9%
7
   4.7%
6
   3.9%
19
   4.2%
Nx
0
   0.0%
3
   2.0%
3
   2.0%
6
   1.3%
[1]
Measure Description: Clinical N stage is an evaluation/staging of LN status through physical examination. N0, no regional LN metastasis; N1, metastasis to movable ipsilateral axillary LNs (IALNs); N2a, metastasis in IALNs fixed to one another (matted) or the other structures; N2b, metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary LN metastasis; N3a, metastasis in ipsilateral infraclavicular LNs; N3b, metastasis in ipsilateral internal mammary LNs fixed and axillary LN; N3c, metastasis in ipsilateral subclavicar LNs; Nx, not assessed.
Number of participants with the indicated IHC results   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Not applicable
60
  39.0%
53
  35.6%
61
  40.1%
174
  38.2%
Equivocal: Score of 2+
9
   5.8%
5
   3.4%
8
   5.3%
22
   4.8%
Positive: Score of 3+
81
  52.6%
89
  59.7%
76
  50.0%
246
  54.1%
Negative: Score of 0-1+
0
   0.0%
1
   0.7%
3
   2.0%
4
   0.9%
Non interpretable
4
   2.6%
1
   0.7%
4
   2.6%
9
   2.0%
[1]
Measure Description: An Immunohistochemistry (IHC) test gives a score of 0 to 3+, which indicates the amount of Human Epidermal Growth Factor (HER2) receptor proteins on the cancer cells in the sample tissue. A positive score (3+) indicates that HER2 receptor protein is present, a negative score (0-1+) indicates that no HER2 receptor protein is present, and an equivocal score (2+) indicates uncertainty and a result that is open for interpretation. Equivocal results require additional testing. "Not applicable" refers to the number of participants who did not have IHC testing done.
Number of participants with the indicated FISH results   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 154 participants 149 participants 152 participants 455 participants
Not applicable
38
  24.7%
42
  28.2%
41
  27.0%
121
  26.6%
Amplified
115
  74.7%
105
  70.5%
109
  71.7%
329
  72.3%
Not amplified
1
   0.6%
2
   1.3%
1
   0.7%
4
   0.9%
Not interpretable
0
   0.0%
0
   0.0%
1
   0.7%
1
   0.2%
[1]
Measure Description: The Fluorescent In Situ Hybridization (FISH) assay was used to determine the overexpression and/or amplification of HER2 in the invasive component of the primary tumor. Amplified indicates that the cell is overexpressing copies of the HER2 gene. Not amplified indicates that there is no overexpression of copies of the HER2 gene. "Not applicable" refers to the number of participants who did not have the FISH assay performed.
1.Primary Outcome
Title Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery
Hide Description Pathological complete response is defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to National Surgical Adjuvant Breast and Bowel Project (NSABP) guidelines, which do not take into account the histological nodal status.
Time Frame Weeks 20 to 22
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
38 44 78
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib 1500 mg, Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3416
Comments [Not Specified]
Method Binomial
Comments Binomial p-value for Trastuzumab 2 mg/kg versus Lapatinib 1500 mg
Method of Estimation Estimation Parameter Percentage of participants with pCR
Estimated Value -4.85
Confidence Interval (2-Sided) 97.5%
-17.6 to 8.16
Estimation Comments Estimation Comments: Estimated value is the difference in the percentage of participants with pCR: Arm1 (Lapatinib 1500 mg) minus Arm2 (Trastuzumab 2 mg/kg).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab 2 mg/kg, Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Binomial
Comments Binomial p-value for Trastuzumab 2 mg/kg versus Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Method of Estimation Estimation Parameter Percentage of participants with pCR
Estimated Value 21.79
Confidence Interval (2-Sided) 97.5%
9.08 to 34.23
Estimation Comments Estimation Comments: Estimated value is the difference in the percentage of participants with pCR: Arm3 (Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg) minus Arm2 (Trastuzumab 2 mg/kg)
2.Secondary Outcome
Title Number of Participants With Overall Response at Week 6
Hide Description The number of participants with overall response (complete response and/or partial response) was evaluated using World Health Organization (WHO) criteria by clinical examination and by mammography and breast echography with bi-dimensional measurements at Week 6. As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
Overall Response 81 45 102
No Change 57 81 33
Progressive Disease 5 11 2
Not Evaluated 7 9 12
Missing Data 4 3 3
3.Secondary Outcome
Title Overall Response at the Time of Surgery
Hide Description The number of participants with overall response (complete response and/or partial response) was evaluated using WHO criteria by clinical examination and mammography and breast echography with bi-dimensional measurements at the time of surgery (Weeks 20 to 22). As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.
Time Frame Time of surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
Overall Response 114 105 122
No Change 8 16 7
Progressive Disease 0 2 1
Not Evaluated 19 20 14
Missing Data 13 6 8
4.Secondary Outcome
Title Number of Participants With Negative Lymph Nodes at the Time of Surgery
Hide Description Participants were assessed for node-negative lymph nodes at the time of surgery. As per the pathological TNM (Tumor, Node, Metastases) classification (pTNM) of malignant tumors: pN, absence or presence and extent of regional lymph node metastasis. Node-negative (pN0) participants had no regional lymph node metastasis. Although not assessed in this measure, pT is the extent of primary tumor, and pM is the absence or presence of distant metastasis.
Time Frame Time of surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants with a lymph node status of pNX (i.e., regional lymph nodes cannot be assessed) were omitted from the analysis of node-negative participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 139 140 137
Measure Type: Number
Unit of Measure: participants
72 82 100
5.Secondary Outcome
Title Number of Participants With Actual Indicated Surgery
Hide Description Participants were assessed for the type of surgery they underwent for breast cancer. Non-conservative surgery is defined as a radical or modified radical mastectomy. Conservative surgery is comprised of a lumpectomy, a quadrantectomy/segmentectomy, or a partial mastectomy. Participants who were not assessed as being candidates for non-conservative or conservative surgery were classified as non-operable.
Time Frame At surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Measure Type: Number
Unit of Measure: participants
Conservative 66 58 63
Non-conservative 77 85 80
Non-operable 11 6 9
6.Secondary Outcome
Title Mean Change From Baseline in Tumor Size at Week 6 and at Surgery
Hide Description Mean change from baseline in tumor in tumor size. Change from baseline in tumor size was defined as tumor size at Week 6/ surgery (Weeks 20 to 22) minus tumor size at baseline. The difference in treatment arms was estimated for Lapatinib 1500 mg versus Trastuzumab 2 mg/kg and for Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg versus Trastuzumab 2 mg/kg.
Time Frame Week 6 and surgery (Weeks 20 to 22)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 154 149 152
Mean (Standard Deviation)
Unit of Measure: millimeters
Week 6 -20.45  (18.43) -13.42  (16.44) -25.77  (19.91)
Surgery (Weeks 20 to 22) -41.01  (23.81) -35.47  (22.95) -43.59  (26.88)
7.Secondary Outcome
Title Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab
Hide Description Participants with progressive disease at 4 week assessment that were permitted to commence treatment with paclitaxel.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants who did not start any treatment were excluded from analysis.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 149 146 149
Measure Type: Number
Unit of Measure: participants
8 12 6
8.Secondary Outcome
Title Event-free Survival (EFS) - Median Clinical Follow-up
Hide Description Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression.
Time Frame From randomization up to approximately year 10
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 152 154 149
Median (95% Confidence Interval)
Unit of Measure: years
9.69
(9.55 to 9.73)
9.60
(8.21 to 9.69)
9.66
(9.50 to 9.72)
9.Secondary Outcome
Title Event-free Survival (EFS) - Events and Censoring
Hide Description Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression.
Time Frame From randomization up to approximately year 10
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 152 154 149
Measure Type: Number
Unit of Measure: Number of Participants
Number of subjects with EFS events 43 47 47
Number of subjects censored - total 109 107 102
Number of subjects censored - Clinical follow-up ongoing 0 0 0
Number of subjects censored - Clinical follow-up ended - total 103 105 99
Number of subjects censored -Clinical follow-up ended - Completed study follow-up 61 49 58
Number of subjects censored - Clinical follow-up ended - Lost to follow-up 17 20 10
Number of subjects censored - Clinical follow-up ended - Withdrew (but consent for survival f/u) 3 6 4
Number of subjects censored - Clinical follow-up ended - Withdrew 22 30 27
Number of subjects censored - Other 6 2 3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg, Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.548
Comments The two-sided stratified log-rank test was implemented as the score test from the Cox model.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.878
Confidence Interval (2-Sided) 95%
0.57 to 1.34
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate hazard ratios and corresponding confidence intervals for the pairwise comparisons of individual treatment arms with the trastuzumab alone arm.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lapatinib 1500 mg, Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.981
Comments The two-sided stratified log-rank test was implemented as the score test from the Cox model.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.005
Confidence Interval (2-Sided) 95%
0.66 to 1.52
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate hazard ratios and corresponding confidence intervals for the pairwise comparisons of individual treatment arms with the trastuzumab alone arm.
10.Secondary Outcome
Title Overall Survival (OS) - Median Survival Follow-up
Hide Description Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study.
Time Frame From randomization up to approximately year 10
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 152 154 149
Median (95% Confidence Interval)
Unit of Measure: years
9.70
(9.60 to 9.76)
9.62
(8.86 to 9.67)
9.64
(9.35 to 9.71)
11.Secondary Outcome
Title Overall Survival (OS) - Deaths and Censoring
Hide Description Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study.
Time Frame From randomization up to approximately year 10
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 152 154 149
Measure Type: Number
Unit of Measure: Number of Participants
Number of deaths due to any cause 26 31 32
Number of subjects censored - total 126 123 117
Number of subjects censored - Survival follow-up ongoing 0 0 0
Number of subjects censored - Survival follow-up ended - total 120 121 114
Number of subjects censored -Survival follow-up ended - Completed study follow-up 74 59 62
Number of subjects censored - Survival follow-up ended - Lost to follow-up 22 27 18
Number of subjects censored - Survival follow-up ended - Withdrew 24 35 34
Number of subjects censored - Other 6 2 3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg, Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.379
Comments The two-sided stratified log-rank test was implemented as the score test from the Cox model.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.788
Confidence Interval (2-Sided) 95%
0.46 to 1.34
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate hazard ratios and corresponding confidence intervals for the pairwise comparisons of individual treatment arms with the trastuzumab alone arm.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lapatinib 1500 mg, Trastuzumab 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.880
Comments The two-sided stratified log-rank test was implemented as the score test from the Cox model.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.962
Confidence Interval (2-Sided) 95%
0.58 to 1.60
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate hazard ratios and corresponding confidence intervals for the pairwise comparisons of individual treatment arms with the trastuzumab alone arm.
12.Secondary Outcome
Title Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population)
Hide Description The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis
Time Frame up to year 10
Hide Outcome Measure Data
Hide Analysis Population Description
For EFS, the landmark population was the subset of the ITT population who have not had an EFS event within 30 weeks after randomization and were still in clinical follow-up.
Arm/Group Title Pathological Complete Response (pCR) No Pathological Complete Response (pCR) Overall
Hide Arm/Group Description:
locoregional pathological Complete Response (pCR)
no locoregional pathological Complete Response (pCR)
Overall - of the 3 arms
Overall Number of Participants Analyzed 136 274 410
Median (95% Confidence Interval)
Unit of Measure: years
All subjects in the EFS landmark analysis with EFS events
9.05
(8.86 to 9.14)
9.11
(9.05 to 9.14)
9.09
(9.03 to 9.13)
Subjects in the EFS landmark analysis in the lapatinib + trastuzumab arm with EFS events
9.13
(8.97 to 9.23)
9.10
(7.24 to 9.15)
9.12
(8.97 to 9.15)
Subjects in the EFS landmark analysis in the lapatinib arm with EFS events
8.08
(6.08 to 9.12)
9.09
(8.52 to 9.19)
9.05
(8.23 to 9.12)
Subjects in the EFS landmark analysis in the trastuzumab arm with EFS events
8.98
(8.38 to 9.21)
9.12
(9.03 to 9.25)
9.11
(8.96 to 9.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Overall - All subjects in the EFS landmark analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00079
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.481
Confidence Interval (2-Sided) 95%
0.31 to 0.73
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Subjects in the EFS landmark analysis in the lapatinib + trastuzumab arm
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.350
Confidence Interval (2-Sided) 95%
0.16 to 0.71
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Subjects in the EFS landmark analysis in the lapatinib arm
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.532
Confidence Interval (2-Sided) 95%
0.21 to 1.16
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Subjects in the EFS landmark analysis in the trastuzumab arm
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.163
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.601
Confidence Interval (2-Sided) 95%
0.28 to 1.20
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
13.Secondary Outcome
Title Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population)
Hide Description The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis
Time Frame up to year 10
Hide Outcome Measure Data
Hide Analysis Population Description
For EFS, the landmark population was the subset of the ITT population who have not had an EFS event within 30 weeks after randomization and were still in clinical follow-up.
Arm/Group Title Pathological Complete Response (pCR) No Pathological Complete Response (pCR) Overall
Hide Arm/Group Description:
locoregional pathological Complete Response (pCR)
no locoregional pathological Complete Response (pCR)
Overall - of the 3 arms
Overall Number of Participants Analyzed 136 274 410
Measure Type: Number
Unit of Measure: Number of participants
All subjects in the EFS landmark analysis with EFS events 29 98 127
Subjects in the EFS landmark analysis in the lapatinib + trastuzumab arm with EFS events 11 28 39
Subjects in the EFS landmark analysis in the lapatinib arm with EFS events 7 36 43
Subjects in the EFS landmark analysis in the trastuzumab arm with EFS events 11 34 45
14.Secondary Outcome
Title Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population)
Hide Description The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis
Time Frame up to year 10
Hide Outcome Measure Data
Hide Analysis Population Description
For OS, the landmark population was the subset of the ITT population who were alive and were followed up for overall survival 30 weeks after randomization.
Arm/Group Title Pathological Complete Response (pCR) No Pathological Complete Response (pCR) Overall
Hide Arm/Group Description:
locoregional pathological Complete Response (pCR)
no locoregional pathological Complete Response (pCR)
Overall - of the 3 arms
Overall Number of Participants Analyzed 137 283 420
Median (95% Confidence Interval)
Unit of Measure: years
All subjects in the OS landmark analysis who died
9.10
(8.97 to 9.18)
9.09
(9.03 to 9.12)
9.09
(9.04 to 9.13)
Subjects in the OS landmark analysis in the lapatinib + trastuzumab arm who died
9.14
(9.05 to 9.24)
9.09
(7.95 to 9.15)
9.12
(9.05 to 9.16)
Subjects in the OS landmark analysis in the lapatinib arm who died
8.31
(7.24 to 9.15)
9.08
(8.95 to 9.14)
9.07
(8.50 to 9.12)
Subjects in the OS landmark analysis in the trastuzumab arm who died
8.98
(8.02 to 9.21)
9.09
(8.51 to 9.15)
9.07
(8.86 to 9.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Overall - All subjects in the OS landmark analysis
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00041
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.366
Confidence Interval (2-Sided) 95%
0.20 to 0.63
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Subjects in the OS landmark analysis in the lapatinib + trastuzumab arm
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.223
Confidence Interval (2-Sided) 95%
0.07 to 0.58
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Subjects in the OS landmark analysis in the lapatinib arm
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.125
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.433
Confidence Interval (2-Sided) 95%
0.12 to 1.17
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pathological Complete Response (pCR), No Pathological Complete Response (pCR)
Comments Subjects in the OS landmark analysis in the trastuzumab arm
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.414
Confidence Interval (2-Sided) 95%
0.15 to 1.00
Estimation Comments Cox models (Cox, 1972), with the stratification factors entered as strata variables, were used to calculate a hazard ratio and corresponding confidence interval comparing pCR and no pCR.
15.Secondary Outcome
Title Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants With OS Events (OS Landmark Population)
Hide Description The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis
Time Frame up to year 10
Hide Outcome Measure Data
Hide Analysis Population Description
For OS, the landmark population was the subset of the ITT population who were alive and were followed up for overall survival 30 weeks after randomization.
Arm/Group Title Pathological Complete Response (pCR) No Pathological Complete Response (pCR) Overall
Hide Arm/Group Description:
locoregional pathological Complete Response (pCR)
no locoregional pathological Complete Response (pCR)
Overall - of the 3 arms
Overall Number of Participants Analyzed 137 283 420
Measure Type: Number
Unit of Measure: Number of Participants
All participants in the OS landmark analysis who died 15 70 85
Participants in the OS landmark analysis in the lapatinib + trastuzumab arm who died 5 19 24
Participants in the OS landmark analysis in the lapatinib arm who died 4 26 30
Participants in the OS landmark analysis in the trastuzumab arm who died 6 25 31
16.Secondary Outcome
Title To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints
Hide Description [Not Specified]
Time Frame Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 31 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 149 151 148
Measure Type: Count of Participants
Unit of Measure: Participants
2
   1.3%
0
   0.0%
1
   0.7%
17.Secondary Outcome
Title Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT)
Hide Description Metabolic Response Rate determined by Positron Emission Tomography/Computed Tomography (PET/CT)
Time Frame Week 2 and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Translational Data Set. Note that evaluable samples were not available for all participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 26 26 25
Measure Type: Number
Unit of Measure: Percentage of participants
Metabolic Response Rate (%) Determined by PET/CT at week 2 66.7 56.5 95.0
Metabolic Response Rate (%) Determined by PET/CT at week 6 60.9 43.5 78.9
18.Secondary Outcome
Title Percentage of Participants With the Indicated Biomarker Expression - PIK3CA.
Hide Description Biomarker levels of phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) were assessed in participants at baseline.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Translational Data Set. Note that evaluable samples were not available for all participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 124 112 119
Measure Type: Number
Unit of Measure: Percentage of participants
23 19 25
19.Secondary Outcome
Title Percentage of Participants With the Indicated Biomarker Expression - PTEN.
Hide Description Biomarker levels of phosphate and tensin homolog deleted from chromosome 10 (PTEN) were assessed in participants at baseline.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Translational Data Set. Note that evaluable samples were not available for all participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 123 114 112
Measure Type: Number
Unit of Measure: Percentage of participants
Biomarker: PTEN by Cell Signalling Technology - PTEN Normal (%) 74 70 75
Biomarker: PTEN by Cell Signalling Technology - PTEN Loss (%) 26 30 25
20.Secondary Outcome
Title Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR
Hide Description Ratio (95% CI) of geometric means in p95 human epidermal growth factor receptor (p95HER2) expression in hormone-receptor (HR) positive patients with pathological complete response (pCR) vs no pCR
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Translational Data Set. Note that evaluable samples were not available for all participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 97 93 91
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.0
(0.50 to 1.87)
1.6
(1.0 to 2.71)
2.1
(1.2 to 3.7)
21.Secondary Outcome
Title Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream
Hide Description Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. In the adjuvant phase, after surgery all participants received 3 courses of adjuvant 5-fluorouracil, epirubicin and cyclophosphamide, followed by lapatinib 1500 mg or trastuzumab 2 mg/kg or lapatinib 1000/750 mg plus trastuzumab 2 mg/kg given prior to surgery in the neoadjuvant setting for an additional 34 weeks.
Time Frame Measurement performed at one or more of the time points: baseline, week 2 or week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Translational Data Set. Note that evaluable samples were not available for all participants.
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 19 12 20
Measure Type: Number
Unit of Measure: Percentage of Participants
21 17 25
22.Post-Hoc Outcome
Title All Collected Deaths
Hide Description On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, which was approximately 31 weeks. Deaths post treatment survival follow up were collected after the on treatment period, up to 10 years.
Time Frame on-treatment: up to week 31; post-treatment: up to year 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Lapatinib 1500 mg Trastuzumab 2 mg/kg Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
Hide Arm/Group Description:
Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks
Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
Overall Number of Participants Analyzed 149 151 148
Measure Type: Number
Unit of Measure: Participants
Total Deaths 26 31 32
On-Treatment Deaths 1 2 0
Time Frame Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 31 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Hide Arm/Group Description Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks Oral lapatinib (1500 milligrams [mg] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared [mg/m^2]) intravenous (IV) for an additional 12 weeks Trastuzumab (4 mg/kilograms [kg] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m^2 IV) for an additional 12 weeks
All-Cause Mortality
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/149 (0.67%)   2/151 (1.32%)   0/148 (0.00%) 
Hide Serious Adverse Events
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   61/149 (40.94%)   58/151 (38.41%)   36/148 (24.32%) 
Blood and lymphatic system disorders       
AGRANULOCYTOSIS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
ANAEMIA  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
FEBRILE NEUTROPENIA  1  3/149 (2.01%)  2/151 (1.32%)  8/148 (5.41%) 
LEUKOPENIA  1  2/149 (1.34%)  0/151 (0.00%)  1/148 (0.68%) 
NEUTROPENIA  1  14/149 (9.40%)  13/151 (8.61%)  16/148 (10.81%) 
PANCYTOPENIA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Cardiac disorders       
CARDIAC FAILURE CONGESTIVE  1  3/149 (2.01%)  0/151 (0.00%)  1/148 (0.68%) 
CARDIO-RESPIRATORY ARREST  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
MYOCARDIAL INFARCTION  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Gastrointestinal disorders       
DIARRHOEA  1  9/149 (6.04%)  9/151 (5.96%)  0/148 (0.00%) 
DUODENITIS  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
ENTERITIS  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
GASTRITIS EROSIVE  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
INGUINAL HERNIA  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
NAUSEA  1  2/149 (1.34%)  1/151 (0.66%)  1/148 (0.68%) 
PANCREATITIS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
VOMITING  1  3/149 (2.01%)  1/151 (0.66%)  2/148 (1.35%) 
General disorders       
ASTHENIA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
CHEST DISCOMFORT  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
CHEST PAIN  1  1/149 (0.67%)  1/151 (0.66%)  0/148 (0.00%) 
GENERAL PHYSICAL HEALTH DETERIORATION  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
PYREXIA  1  5/149 (3.36%)  2/151 (1.32%)  2/148 (1.35%) 
Hepatobiliary disorders       
CHOLECYSTITIS ACUTE  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
HEPATITIS ACUTE  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
HYPERBILIRUBINAEMIA  1  4/149 (2.68%)  4/151 (2.65%)  0/148 (0.00%) 
HYPERTRANSAMINASAEMIA  1  15/149 (10.07%)  23/151 (15.23%)  3/148 (2.03%) 
Infections and infestations       
APPENDICITIS  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
BACTERIAL SEPSIS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
BREAST CELLULITIS  1  1/149 (0.67%)  0/151 (0.00%)  1/148 (0.68%) 
CELLULITIS  1  2/149 (1.34%)  1/151 (0.66%)  2/148 (1.35%) 
CELLULITIS STAPHYLOCOCCAL  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
DEVICE RELATED INFECTION  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
DEVICE RELATED SEPSIS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
ERYSIPELAS  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
HEPATITIS B  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
HERPES SIMPLEX  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
HERPES ZOSTER  1  0/149 (0.00%)  1/151 (0.66%)  1/148 (0.68%) 
MASTITIS  1  1/149 (0.67%)  2/151 (1.32%)  0/148 (0.00%) 
PHARYNGITIS  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
PNEUMONIA  1  2/149 (1.34%)  0/151 (0.00%)  2/148 (1.35%) 
SKIN INFECTION  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
URINARY TRACT INFECTION  1  0/149 (0.00%)  3/151 (1.99%)  0/148 (0.00%) 
VASCULAR DEVICE INFECTION  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
WOUND INFECTION  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Injury, poisoning and procedural complications       
ACCIDENTAL OVERDOSE  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
INFUSION RELATED REACTION  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
LUMBAR VERTEBRAL FRACTURE  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
POISONING  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
SEROMA  1  1/149 (0.67%)  1/151 (0.66%)  1/148 (0.68%) 
SPINAL FRACTURE  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
TOXICITY TO VARIOUS AGENTS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
TRANSFUSION REACTION  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Investigations       
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
Metabolism and nutrition disorders       
DEHYDRATION  1  0/149 (0.00%)  2/151 (1.32%)  0/148 (0.00%) 
DIABETES MELLITUS  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
HYPERPHOSPHATASAEMIA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
HYPOGLYCAEMIA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
HYPOKALAEMIA  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
Musculoskeletal and connective tissue disorders       
OSTEOPOROTIC FRACTURE  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
ROTATOR CUFF SYNDROME  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
LOBULAR BREAST CARCINOMA IN SITU  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
UTERINE LEIOMYOMA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Nervous system disorders       
HEADACHE  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
NEUROPATHY PERIPHERAL  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
SCIATICA  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
Renal and urinary disorders       
ACUTE KIDNEY INJURY  1  2/149 (1.34%)  1/151 (0.66%)  0/148 (0.00%) 
NEPHRECTASIA  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
NEPHROLITHIASIS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
Reproductive system and breast disorders       
METRORRHAGIA  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
VULVOVAGINAL PRURITUS  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
ASTHMA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
INTERSTITIAL LUNG DISEASE  1  2/149 (1.34%)  0/151 (0.00%)  0/148 (0.00%) 
ORGANISING PNEUMONIA  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
PNEUMONITIS  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
PNEUMOTHORAX  1  0/149 (0.00%)  1/151 (0.66%)  0/148 (0.00%) 
PULMONARY EMBOLISM  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Skin and subcutaneous tissue disorders       
BLISTER  1  1/149 (0.67%)  0/151 (0.00%)  0/148 (0.00%) 
Vascular disorders       
JUGULAR VEIN THROMBOSIS  1  0/149 (0.00%)  0/151 (0.00%)  1/148 (0.68%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Lapatinib 1500 mg Trastuzumab 2 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   147/149 (98.66%)   148/151 (98.01%)   141/148 (95.27%) 
Blood and lymphatic system disorders       
ANAEMIA  1  36/149 (24.16%)  33/151 (21.85%)  27/148 (18.24%) 
FEBRILE NEUTROPENIA  1  3/149 (2.01%)  0/151 (0.00%)  1/148 (0.68%) 
LEUKOPENIA  1  21/149 (14.09%)  18/151 (11.92%)  10/148 (6.76%) 
LYMPHOPENIA  1  5/149 (3.36%)  2/151 (1.32%)  6/148 (4.05%) 
NEUTROPENIA  1  47/149 (31.54%)  51/151 (33.77%)  37/148 (25.00%) 
THROMBOCYTOPENIA  1  4/149 (2.68%)  2/151 (1.32%)  1/148 (0.68%) 
Cardiac disorders       
CARDIAC FAILURE CONGESTIVE  1  3/149 (2.01%)  0/151 (0.00%)  1/148 (0.68%) 
LEFT VENTRICULAR DYSFUNCTION  1  4/149 (2.68%)  0/151 (0.00%)  2/148 (1.35%) 
PALPITATIONS  1  6/149 (4.03%)  6/151 (3.97%)  3/148 (2.03%) 
TACHYCARDIA  1  4/149 (2.68%)  2/151 (1.32%)  4/148 (2.70%) 
Ear and labyrinth disorders       
EAR PAIN  1  3/149 (2.01%)  1/151 (0.66%)  1/148 (0.68%) 
TINNITUS  1  6/149 (4.03%)  1/151 (0.66%)  3/148 (2.03%) 
VERTIGO  1  11/149 (7.38%)  7/151 (4.64%)  6/148 (4.05%) 
Eye disorders       
DRY EYE  1  4/149 (2.68%)  1/151 (0.66%)  2/148 (1.35%) 
LACRIMATION INCREASED  1  3/149 (2.01%)  3/151 (1.99%)  1/148 (0.68%) 
VISUAL IMPAIRMENT  1  2/149 (1.34%)  2/151 (1.32%)  3/148 (2.03%) 
Gastrointestinal disorders       
ABDOMINAL DISCOMFORT  1  3/149 (2.01%)  1/151 (0.66%)  4/148 (2.70%) 
ABDOMINAL DISTENSION  1  10/149 (6.71%)  8/151 (5.30%)  5/148 (3.38%) 
ABDOMINAL PAIN  1  21/149 (14.09%)  28/151 (18.54%)  13/148 (8.78%) 
ABDOMINAL PAIN UPPER  1  23/149 (15.44%)  27/151 (17.88%)  16/148 (10.81%) 
ANAL INFLAMMATION  1  4/149 (2.68%)  2/151 (1.32%)  1/148 (0.68%) 
CONSTIPATION  1  18/149 (12.08%)  15/151 (9.93%)  15/148 (10.14%) 
DIARRHOEA  1  128/149 (85.91%)  123/151 (81.46%)  52/148 (35.14%) 
DRY MOUTH  1  9/149 (6.04%)  5/151 (3.31%)  3/148 (2.03%) 
DYSPEPSIA  1  17/149 (11.41%)  26/151 (17.22%)  10/148 (6.76%) 
DYSPHAGIA  1  3/149 (2.01%)  0/151 (0.00%)  3/148 (2.03%) 
EPIGASTRIC DISCOMFORT  1  3/149 (2.01%)  2/151 (1.32%)  2/148 (1.35%) 
FLATULENCE  1  3/149 (2.01%)  5/151 (3.31%)  2/148 (1.35%) 
GASTRITIS  1  2/149 (1.34%)  8/151 (5.30%)  3/148 (2.03%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  5/149 (3.36%)  2/151 (1.32%)  0/148 (0.00%) 
HAEMORRHOIDS  1  13/149 (8.72%)  10/151 (6.62%)  10/148 (6.76%) 
MOUTH ULCERATION  1  12/149 (8.05%)  4/151 (2.65%)  1/148 (0.68%) 
NAUSEA  1  75/149 (50.34%)  81/151 (53.64%)  76/148 (51.35%) 
RECTAL HAEMORRHAGE  1  4/149 (2.68%)  2/151 (1.32%)  0/148 (0.00%) 
STOMATITIS  1  27/149 (18.12%)  18/151 (11.92%)  23/148 (15.54%) 
TOOTHACHE  1  4/149 (2.68%)  1/151 (0.66%)  2/148 (1.35%) 
VOMITING  1  54/149 (36.24%)  57/151 (37.75%)  38/148 (25.68%) 
General disorders       
ASTHENIA  1  39/149 (26.17%)  47/151 (31.13%)  35/148 (23.65%) 
AXILLARY PAIN  1  5/149 (3.36%)  0/151 (0.00%)  3/148 (2.03%) 
CHEST DISCOMFORT  1  0/149 (0.00%)  3/151 (1.99%)  6/148 (4.05%) 
CHEST PAIN  1  5/149 (3.36%)  5/151 (3.31%)  6/148 (4.05%) 
CHILLS  1  11/149 (7.38%)  3/151 (1.99%)  6/148 (4.05%) 
FACE OEDEMA  1  3/149 (2.01%)  5/151 (3.31%)  4/148 (2.70%) 
FATIGUE  1  52/149 (34.90%)  45/151 (29.80%)  38/148 (25.68%) 
FEELING COLD  1  0/149 (0.00%)  1/151 (0.66%)  3/148 (2.03%) 
GENERALISED OEDEMA  1  1/149 (0.67%)  3/151 (1.99%)  3/148 (2.03%) 
INFLUENZA LIKE ILLNESS  1  3/149 (2.01%)  2/151 (1.32%)  2/148 (1.35%) 
MUCOSAL DRYNESS  1  3/149 (2.01%)  2/151 (1.32%)  2/148 (1.35%) 
MUCOSAL EROSION  1  3/149 (2.01%)  0/151 (0.00%)  0/148 (0.00%) 
MUCOSAL INFLAMMATION  1  36/149 (24.16%)  34/151 (22.52%)  22/148 (14.86%) 
OEDEMA  1  4/149 (2.68%)  0/151 (0.00%)  11/148 (7.43%) 
OEDEMA PERIPHERAL  1  8/149 (5.37%)  9/151 (5.96%)  13/148 (8.78%) 
PAIN  1  3/149 (2.01%)  6/151 (3.97%)  2/148 (1.35%) 
PERIPHERAL SWELLING  1  4/149 (2.68%)  2/151 (1.32%)  3/148 (2.03%) 
PYREXIA  1  34/149 (22.82%)  23/151 (15.23%)  23/148 (15.54%) 
Hepatobiliary disorders       
HYPERBILIRUBINAEMIA  1  21/149 (14.09%)  26/151 (17.22%)  7/148 (4.73%) 
HYPERTRANSAMINASAEMIA  1  55/149 (36.91%)  55/151 (36.42%)  39/148 (26.35%) 
Immune system disorders       
HYPERSENSITIVITY  1  6/149 (4.03%)  6/151 (3.97%)  7/148 (4.73%) 
SEASONAL ALLERGY  1  3/149 (2.01%)  1/151 (0.66%)  0/148 (0.00%) 
Infections and infestations       
BRONCHITIS  1  2/149 (1.34%)  5/151 (3.31%)  3/148 (2.03%) 
CONJUNCTIVITIS  1  11/149 (7.38%)  8/151 (5.30%)  5/148 (3.38%) 
CYSTITIS  1  8/149 (5.37%)  6/151 (3.97%)  3/148 (2.03%) 
HERPES SIMPLEX  1  3/149 (2.01%)  0/151 (0.00%)  2/148 (1.35%) 
INFLUENZA  1  8/149 (5.37%)  8/151 (5.30%)  9/148 (6.08%) 
LOCALISED INFECTION  1  3/149 (2.01%)  3/151 (1.99%)  0/148 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION  1  3/149 (2.01%)  1/151 (0.66%)  1/148 (0.68%) 
MASTITIS  1  2/149 (1.34%)  1/151 (0.66%)  3/148 (2.03%) 
NAIL INFECTION  1  8/149 (5.37%)  1/151 (0.66%)  0/148 (0.00%) 
NASOPHARYNGITIS  1  11/149 (7.38%)  12/151 (7.95%)  11/148 (7.43%) 
ORAL HERPES  1  2/149 (1.34%)  0/151 (0.00%)  3/148 (2.03%) 
PARONYCHIA  1  17/149 (11.41%)  14/151 (9.27%)  2/148 (1.35%) 
PHARYNGITIS  1  4/149 (2.68%)  7/151 (4.64%)  5/148 (3.38%) 
PUSTULE  1  3/149 (2.01%)  1/151 (0.66%)  1/148 (0.68%) 
RHINITIS  1  6/149 (4.03%)  4/151 (2.65%)  5/148 (3.38%) 
SINUSITIS  1  3/149 (2.01%)  5/151 (3.31%)  2/148 (1.35%) 
SKIN INFECTION  1  4/149 (2.68%)  1/151 (0.66%)  2/148 (1.35%) 
TONSILLITIS  1  0/149 (0.00%)  3/151 (1.99%)  4/148 (2.70%) 
UPPER RESPIRATORY TRACT INFECTION  1  10/149 (6.71%)  9/151 (5.96%)  14/148 (9.46%) 
URINARY TRACT INFECTION  1  11/149 (7.38%)  14/151 (9.27%)  6/148 (4.05%) 
VAGINAL INFECTION  1  5/149 (3.36%)  1/151 (0.66%)  2/148 (1.35%) 
VIRAL INFECTION  1  0/149 (0.00%)  0/151 (0.00%)  3/148 (2.03%) 
Injury, poisoning and procedural complications       
RADIATION SKIN INJURY  1  16/149 (10.74%)  11/151 (7.28%)  18/148 (12.16%) 
SEROMA  1  2/149 (1.34%)  0/151 (0.00%)  6/148 (4.05%) 
THERMAL BURN  1  3/149 (2.01%)  0/151 (0.00%)  1/148 (0.68%) 
WOUND COMPLICATION  1  4/149 (2.68%)  4/151 (2.65%)  6/148 (4.05%) 
Investigations       
EJECTION FRACTION DECREASED  1  6/149 (4.03%)  2/151 (1.32%)  4/148 (2.70%) 
GAMMA-GLUTAMYLTRANSFERASE  1  3/149 (2.01%)  2/151 (1.32%)  0/148 (0.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  3/149 (2.01%)  7/151 (4.64%)  1/148 (0.68%) 
NEUTROPHIL COUNT INCREASED  1  3/149 (2.01%)  1/151 (0.66%)  2/148 (1.35%) 
WEIGHT DECREASED  1  8/149 (5.37%)  10/151 (6.62%)  1/148 (0.68%) 
WEIGHT INCREASED  1  2/149 (1.34%)  2/151 (1.32%)  3/148 (2.03%) 
Metabolism and nutrition disorders       
DECREASED APPETITE  1  35/149 (23.49%)  39/151 (25.83%)  17/148 (11.49%) 
DEHYDRATION  1  1/149 (0.67%)  5/151 (3.31%)  0/148 (0.00%) 
HYPERCHOLESTEROLAEMIA  1  0/149 (0.00%)  1/151 (0.66%)  3/148 (2.03%) 
HYPERGLYCAEMIA  1  3/149 (2.01%)  0/151 (0.00%)  4/148 (2.70%) 
HYPERPHOSPHATASAEMIA  1  22/149 (14.77%)  22/151 (14.57%)  12/148 (8.11%) 
HYPOKALAEMIA  1  4/149 (2.68%)  3/151 (1.99%)  0/148 (0.00%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  27/149 (18.12%)  26/151 (17.22%)  32/148 (21.62%) 
BACK PAIN  1  22/149 (14.77%)  10/151 (6.62%)  14/148 (9.46%) 
BONE PAIN  1  10/149 (6.71%)  12/151 (7.95%)  18/148 (12.16%) 
JOINT STIFFNESS  1  2/149 (1.34%)  1/151 (0.66%)  4/148 (2.70%) 
MUSCLE SPASMS  1  6/149 (4.03%)  4/151 (2.65%)  3/148 (2.03%) 
MUSCULOSKELETAL CHEST PAIN  1  4/149 (2.68%)  2/151 (1.32%)  1/148 (0.68%) 
MUSCULOSKELETAL PAIN  1  8/149 (5.37%)  16/151 (10.60%)  11/148 (7.43%) 
MUSCULOSKELETAL STIFFNESS  1  1/149 (0.67%)  1/151 (0.66%)  3/148 (2.03%) 
MYALGIA  1  31/149 (20.81%)  33/151 (21.85%)  34/148 (22.97%) 
NECK PAIN  1  7/149 (4.70%)  5/151 (3.31%)  5/148 (3.38%) 
OSTEOPOROSIS  1  0/149 (0.00%)  1/151 (0.66%)  3/148 (2.03%) 
PAIN IN EXTREMITY  1  13/149 (8.72%)  20/151 (13.25%)  13/148 (8.78%) 
Nervous system disorders       
AGEUSIA  1  4/149 (2.68%)  3/151 (1.99%)  0/148 (0.00%) 
DIZZINESS  1  13/149 (8.72%)  13/151 (8.61%)  15/148 (10.14%) 
DYSGEUSIA  1  6/149 (4.03%)  6/151 (3.97%)  1/148 (0.68%) 
HEADACHE  1  31/149 (20.81%)  27/151 (17.88%)  26/148 (17.57%) 
HYPOAESTHESIA  1  9/149 (6.04%)  7/151 (4.64%)  12/148 (8.11%) 
MEMORY IMPAIRMENT  1  2/149 (1.34%)  4/151 (2.65%)  2/148 (1.35%) 
NEUROPATHY PERIPHERAL  1  19/149 (12.75%)  21/151 (13.91%)  19/148 (12.84%) 
NEUROTOXICITY  1  3/149 (2.01%)  6/151 (3.97%)  3/148 (2.03%) 
PARAESTHESIA  1  24/149 (16.11%)  15/151 (9.93%)  22/148 (14.86%) 
PERIPHERAL SENSORY NEUROPATHY  1  13/149 (8.72%)  19/151 (12.58%)  14/148 (9.46%) 
POLYNEUROPATHY  1  5/149 (3.36%)  1/151 (0.66%)  3/148 (2.03%) 
TASTE DISORDER  1  9/149 (6.04%)  6/151 (3.97%)  1/148 (0.68%) 
Psychiatric disorders       
ANXIETY  1  7/149 (4.70%)  9/151 (5.96%)  11/148 (7.43%) 
DEPRESSION  1  7/149 (4.70%)  5/151 (3.31%)  9/148 (6.08%) 
INSOMNIA  1  34/149 (22.82%)  23/151 (15.23%)  24/148 (16.22%) 
SLEEP DISORDER  1  5/149 (3.36%)  4/151 (2.65%)  2/148 (1.35%) 
Renal and urinary disorders       
DYSURIA  1  11/149 (7.38%)  6/151 (3.97%)  5/148 (3.38%) 
HAEMATURIA  1  4/149 (2.68%)  0/151 (0.00%)  0/148 (0.00%) 
Reproductive system and breast disorders       
AMENORRHOEA  1  6/149 (4.03%)  3/151 (1.99%)  1/148 (0.68%) 
BREAST DISCHARGE  1  3/149 (2.01%)  0/151 (0.00%)  0/148 (0.00%) 
BREAST PAIN  1  6/149 (4.03%)  5/151 (3.31%)  15/148 (10.14%) 
MENSTRUATION IRREGULAR  1  1/149 (0.67%)  2/151 (1.32%)  3/148 (2.03%) 
PELVIC PAIN  1  0/149 (0.00%)  0/151 (0.00%)  4/148 (2.70%) 
VULVOVAGINAL DRYNESS  1  2/149 (1.34%)  2/151 (1.32%)  3/148 (2.03%) 
VULVOVAGINAL INFLAMMATION  1  0/149 (0.00%)  4/151 (2.65%)  0/148 (0.00%) 
VULVOVAGINAL PRURITUS  1  2/149 (1.34%)  2/151 (1.32%)  4/148 (2.70%) 
Respiratory, thoracic and mediastinal disorders       
COUGH  1  25/149 (16.78%)  17/151 (11.26%)  26/148 (17.57%) 
DYSPHONIA  1  1/149 (0.67%)  5/151 (3.31%)  2/148 (1.35%) 
DYSPNOEA  1  16/149 (10.74%)  11/151 (7.28%)  13/148 (8.78%) 
DYSPNOEA EXERTIONAL  1  6/149 (4.03%)  2/151 (1.32%)  6/148 (4.05%) 
EPISTAXIS  1  37/149 (24.83%)  30/151 (19.87%)  22/148 (14.86%) 
HAEMOPTYSIS  1  0/149 (0.00%)  0/151 (0.00%)  3/148 (2.03%) 
NASAL DRYNESS  1  6/149 (4.03%)  6/151 (3.97%)  2/148 (1.35%) 
NASAL INFLAMMATION  1  5/149 (3.36%)  3/151 (1.99%)  1/148 (0.68%) 
OROPHARYNGEAL PAIN  1  16/149 (10.74%)  20/151 (13.25%)  15/148 (10.14%) 
PRODUCTIVE COUGH  1  3/149 (2.01%)  0/151 (0.00%)  0/148 (0.00%) 
RHINORRHOEA  1  13/149 (8.72%)  6/151 (3.97%)  10/148 (6.76%) 
Skin and subcutaneous tissue disorders       
ACNE  1  22/149 (14.77%)  20/151 (13.25%)  5/148 (3.38%) 
ALOPECIA  1  95/149 (63.76%)  90/151 (59.60%)  96/148 (64.86%) 
DERMATITIS  1  13/149 (8.72%)  13/151 (8.61%)  8/148 (5.41%) 
DERMATITIS ACNEIFORM  1  14/149 (9.40%)  12/151 (7.95%)  4/148 (2.70%) 
DRY SKIN  1  28/149 (18.79%)  29/151 (19.21%)  8/148 (5.41%) 
ECZEMA  1  6/149 (4.03%)  4/151 (2.65%)  2/148 (1.35%) 
ERYTHEMA  1  14/149 (9.40%)  14/151 (9.27%)  15/148 (10.14%) 
EXFOLIATIVE RASH  1  8/149 (5.37%)  4/151 (2.65%)  0/148 (0.00%) 
HYPERHIDROSIS  1  2/149 (1.34%)  1/151 (0.66%)  3/148 (2.03%) 
NAIL DISORDER  1  36/149 (24.16%)  26/151 (17.22%)  18/148 (12.16%) 
NAIL DYSTROPHY  1  3/149 (2.01%)  2/151 (1.32%)  1/148 (0.68%) 
ONYCHALGIA  1  3/149 (2.01%)  3/151 (1.99%)  1/148 (0.68%) 
ONYCHOLYSIS  1  7/149 (4.70%)  0/151 (0.00%)  2/148 (1.35%) 
PAIN OF SKIN  1  1/149 (0.67%)  4/151 (2.65%)  2/148 (1.35%) 
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  14/149 (9.40%)  14/151 (9.27%)  3/148 (2.03%) 
PRURITUS  1  24/149 (16.11%)  29/151 (19.21%)  9/148 (6.08%) 
RASH  1  67/149 (44.97%)  68/151 (45.03%)  28/148 (18.92%) 
RASH PRURITIC  1  4/149 (2.68%)  3/151 (1.99%)  3/148 (2.03%) 
SCAR PAIN  1  1/149 (0.67%)  3/151 (1.99%)  4/148 (2.70%) 
SKIN EXFOLIATION  1  4/149 (2.68%)  0/151 (0.00%)  1/148 (0.68%) 
SKIN FISSURES  1  13/149 (8.72%)  4/151 (2.65%)  4/148 (2.70%) 
SKIN HYPERPIGMENTATION  1  6/149 (4.03%)  6/151 (3.97%)  2/148 (1.35%) 
SKIN IRRITATION  1  3/149 (2.01%)  1/151 (0.66%)  1/148 (0.68%) 
SKIN LESION  1  5/149 (3.36%)  1/151 (0.66%)  0/148 (0.00%) 
SKIN REACTION  1  2/149 (1.34%)  4/151 (2.65%)  0/148 (0.00%) 
Vascular disorders       
FLUSHING  1  1/149 (0.67%)  3/151 (1.99%)  6/148 (4.05%) 
HAEMATOMA  1  3/149 (2.01%)  1/151 (0.66%)  1/148 (0.68%) 
HOT FLUSH  1  22/149 (14.77%)  15/151 (9.93%)  21/148 (14.19%) 
HYPERTENSION  1  5/149 (3.36%)  5/151 (3.31%)  8/148 (5.41%) 
HYPOTENSION  1  8/149 (5.37%)  5/151 (3.31%)  2/148 (1.35%) 
LYMPHOEDEMA  1  3/149 (2.01%)  5/151 (3.31%)  3/148 (2.03%) 
PHLEBITIS  1  2/149 (1.34%)  3/151 (1.99%)  5/148 (3.38%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@Novartis.com
Publications:
Baselga J, Piccart M, Gelber R, di CosimoS, Viale G, Koehler M, Rojo F. Neo-ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) study [BIG 1-06 /solti/EGF106903]: a phase III translational study for HER2-overexpressing early breast cancer. [Lancet]. 2012;S140-6736(11):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00553358    
Other Study ID Numbers: EGF106903
2006-000564-81 ( EudraCT Number )
CLAP016B2302 ( Other Identifier: Novartis )
First Submitted: November 1, 2007
First Posted: November 4, 2007
Results First Submitted: May 26, 2011
Results First Posted: October 13, 2011
Last Update Posted: June 3, 2021