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

• ClinicalTrials.gov Identifier: NCT00553358
• Recruitment Status: Completed
• First Posted: November 4, 2007
• Results First Posted: October 13, 2011
• Last Update Posted: September 21, 2021
• Sponsor: Novartis Pharmaceuticals
• 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

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg	Lapatinib 1500 mg	Trastuzumab 2 mg/kg
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

Baseline Characteristics

Arm/Group Title		Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg	Total
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
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.

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery
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

Outcome Measure Data

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
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

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).

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
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

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
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
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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
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
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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
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
Description	Participants with progressive disease at 4 week assessment that were permitted to commence treatment with paclitaxel.
Time Frame	Week 6

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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

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.

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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

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.

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)
Description	The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Clinical follow-up is the period during which the patient is monitored such that all recurrence or second primary malignancy (SPM) or contralateral breast cancer (CBC) events would be reported. Patients are considered in clinical follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death.
Time Frame	up to year 10

Outcome Measure Data

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
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
Median clinical follow-up - all subjects in the EFS landmark analysis	Number Analyzed	136 participants	274 participants	410 participants
		9.05; (8.86 to 9.14)	9.11; (9.05 to 9.14)	9.09; (9.03 to 9.13)
Median clinical follow-up- EFS landmark analysis - lapatinib + trastuzumab arm (n=67,71,138)	Number Analyzed	67 participants	71 participants	138 participants
		9.13; (8.97 to 9.23)	9.10; (7.24 to 9.15)	9.12; (8.97 to 9.15)
Median clinical follow-up - subjects in the EFS landmark analysis - lapatinib arm (n=30,104,134)	Number Analyzed	30 participants	104 participants	134 participants
		8.08; (6.08 to 9.12)	9.09; (8.52 to 9.19)	9.05; (8.23 to 9.12)
Median clinical follow-up - subjects in the EFS landmark analysis - trastuzumab arm (n=39,99,138)	Number Analyzed	39 participants	99 participants	138 participants
		8.98; (8.38 to 9.21)	9.12; (9.03 to 9.25)	9.11; (8.96 to 9.17)

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.

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.

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.

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)
Description	The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. For patients who had breast cancer surgery, EFS events are post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For patients who do not undergo breast cancer surgery, EFS events are death during clinical follow-up or non-completion of any neo-adjuvant investigational product due to disease progression or second primary malignancy or contralateral breast cancer.
Time Frame	up to year 10

Outcome Measure Data

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
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	Number Analyzed	136 participants	274 participants	410 participants
		29	98	127
Subjects in the EFS landmark analysis - lapatinib + trastuzumab arm with EFS events (n=67,71,138)	Number Analyzed	67 participants	71 participants	138 participants
		11	28	39
Subjects in the EFS landmark analysis in the lapatinib arm with EFS events (n=30,104,134)	Number Analyzed	30 participants	104 participants	134 participants
		7	36	43
Subjects in the EFS landmark analysis in the trastuzumab arm with EFS events (n=39,99,138)	Number Analyzed	39 participants	99 participants	138 participants
		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)
Description	The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Patients are considered in survival follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death. For subjects with no death recorded in the database, time to death is censored.
Time Frame	up to year 10

Outcome Measure Data

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
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
Median survival follow-up - All subjects in the OS landmark analysis	Number Analyzed	137 participants	283 participants	420 participants
		9.10; (8.97 to 9.18)	9.09; (9.03 to 9.12)	9.09; (9.04 to 9.13)
Median survival follow-up - OS landmark analysis in the lapatinib + trastuzumab arm (n=67,72,139)	Number Analyzed	67 participants	72 participants	139 participants
		9.14; (9.05 to 9.24)	9.09; (7.95 to 9.15)	9.12; (9.05 to 9.16)
Median survival follow-up - OS landmark analysis in the lapatinib (n=30,109,139)	Number Analyzed	30 participants	109 participants	139 participants
		8.31; (7.24 to 9.15)	9.08; (8.95 to 9.14)	9.07; (8.50 to 9.12)
Median survival follow-up - OS landmark analysis in the trastuzumab arm (n=40,102,142)	Number Analyzed	40 participants	102 participants	142 participants
		8.98; (8.02 to 9.21)	9.09; (8.51 to 9.15)	9.07; (8.86 to 9.14)

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.

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.

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.

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 Who Died (OS Landmark Population)
Description	The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Includes deaths due to any cause.
Time Frame	up to year 10

Outcome Measure Data

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
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	Number Analyzed	137 participants	283 participants	420 participants
		15	70	85
Participants in the OS landmark analysis in the lapatinib + trastuzumab arm who died (n=67,72,139)	Number Analyzed	67 participants	72 participants	139 participants
		5	19	24
Participants in the OS landmark analysis in the lapatinib arm who died (n=30,109,139)	Number Analyzed	30 participants	109 participants	139 participants
		4	26	30
Participants in the OS landmark analysis in the trastuzumab arm who died (n=40,102,142)	Number Analyzed	40 participants	102 participants	142 participants
		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
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.

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg	Lapatinib 1500 mg	Trastuzumab 2 mg/kg
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)
Description	Metabolic Response Rate determined by Positron Emission Tomography/Computed Tomography (PET/CT)
Time Frame	Week 2 and Week 6

Outcome Measure Data

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
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.
Description	Biomarker levels of phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) were assessed in participants at baseline.
Time Frame	Baseline

Outcome Measure Data

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
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.
Description	Biomarker levels of phosphate and tensin homolog deleted from chromosome 10 (PTEN) were assessed in participants at baseline.
Time Frame	Baseline

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

Analysis Population Description

Safety population (for on-treatment deaths) and ITT (for total deaths)

Arm/Group Title		Lapatinib 1500 mg	Trastuzumab 2 mg/kg	Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg
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
Total Deaths	Number Analyzed	154 participants	149 participants	152 participants
		31	32	26
On-Treatment Deaths (n=151,148,149)	Number Analyzed	151 participants	148 participants	149 participants
		2	0	1

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• 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):

Chumsri S, Li Z, Serie DJ, Norton N, Mashadi-Hossein A, Tenner K, Brauer HA, Warren S, Danaher P, Colon-Otero G, Partridge AH, Carey LA, Hilbers F, Van Dooren V, Holmes E, Di Cosimo S, Werner O, Huober JB, Dueck AC, Sotiriou C, Saura C, Moreno-Aspitia A, Knutson KL, Perez EA, Thompson EA. Adaptive immune signature in HER2-positive breast cancer in NCCTG (Alliance) N9831 and NeoALTTO trials. NPJ Breast Cancer. 2022 May 24;8(1):68. doi: 10.1038/s41523-022-00430-0.

Pizzamiglio S, Cosentino G, Ciniselli CM, De Cecco L, Cataldo A, Plantamura I, Triulzi T, El-Abed S, Wang Y, Bajji M, Nuciforo P, Huober J, Ellard SL, Rimm DL, Gombos A, Daidone MG, Verderio P, Tagliabue E, Di Cosimo S, Iorio MV. What if the future of HER2-positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study. Cancer Med. 2022 Jan;11(2):332-339. doi: 10.1002/cam4.4449. Epub 2021 Dec 17.

Powles RL, Redmond D, Sotiriou C, Loi S, Fumagalli D, Nuciforo P, Harbeck N, de Azambuja E, Sarp S, Di Cosimo S, Huober J, Baselga J, Piccart-Gebhart M, Elemento O, Pusztai L, Hatzis C. Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):e181564. doi: 10.1001/jamaoncol.2018.1564. Epub 2018 Nov 8.

Fumagalli D, Venet D, Ignatiadis M, Azim HA Jr, Maetens M, Rothe F, Salgado R, Bradbury I, Pusztai L, Harbeck N, Gomez H, Chang TW, Coccia-Portugal MA, Di Cosimo S, de Azambuja E, de la Pena L, Nuciforo P, Brase JC, Huober J, Baselga J, Piccart M, Loi S, Sotiriou C. RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncol. 2017 Feb 1;3(2):227-234. doi: 10.1001/jamaoncol.2016.3824. Erratum In: JAMA Oncol. 2019 Jan 1;5(1):122.

Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, Piccart-Gebhart MJ, Michiels S, Bradbury I, Sotiriou C, Loi S. Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial. JAMA Oncol. 2015 Jul;1(4):448-54. doi: 10.1001/jamaoncol.2015.0830. Erratum In: JAMA Oncol. 2015 Jul;1(4):544. JAMA Oncol. 2015 Nov;1(8):1172. Nucifero, Paolo [corrected to Nuciforo, Paolo]. JAMA Oncol. 2019 Jan 1;5(1):122.

Nuciforo PG, Aura C, Holmes E, Prudkin L, Jimenez J, Martinez P, Ameels H, de la Pena L, Ellis C, Eidtmann H, Piccart-Gebhart MJ, Scaltriti M, Baselga J. Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status. Ann Oncol. 2015 Jul;26(7):1494-500. doi: 10.1093/annonc/mdv175. Epub 2015 Apr 7.

de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. doi: 10.1016/S1470-2045(14)70320-1. Epub 2014 Aug 14.

Yarden Y, Pines G. The ERBB network: at last, cancer therapy meets systems biology. Nat Rev Cancer. 2012 Jul 12;12(8):553-63. doi: 10.1038/nrc3309.

Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horvath Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. doi: 10.1016/S0140-6736(11)61847-3. Epub 2012 Jan 17. Erratum In: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.

• 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: September 21, 2021