Trial Outcomes & Findings for Evaluation of Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer (NCT NCT02213042)

Last Updated: 2021-10-13

Results Overview

Evaluate changes in biomarkers associated with immunomodulation between pre-treatment biopsy and disease progression biopsy within each arm. Biomarker analysis was performed using an mRNA gene expression panel derived from Nanostring platform in a total of 20 subjects who received the study treatment as per the study design and with baseline tumor biopsies available. For the selected biomarkers associated with immunomodulation, the median fold changes of gene expression level and 95% confidence interval are presented. The fold change was calculated as the ratio of the expression level of a biomarker at disease progression over the baseline.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

At screening and at disease progression, assessed up to approx. 3.5 years

Results posted on

2021-10-13

Participant Flow

Overall, 225 subjects were planned and 42 subjects were enrolled in this study

This study was designed to address the post-authorization measures as agreed with the Committee for Medicinal Products for Human Use (CHMP). Recruitment of subjects into this study was challenging, and following agreement with the European Medicines Agency (EMA) enrollment into this study was halted after the enrollment of 42 of the 225 planned subjects.

Participant milestones

Participant milestones
Measure	LAP+TRAS±AI (HER2-Enriched) - Arm A Lapatinib 1000mg + Trastuzumab in HER2 Enriched In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.	TRAS+CHEM±AI (HER2-Enriched) - Arm B Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Overall Study STARTED	17	15	10
Overall Study Total Deaths	11	9	6
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	17	15	10

Reasons for withdrawal

Reasons for withdrawal
Measure	LAP+TRAS±AI (HER2-Enriched) - Arm A Lapatinib 1000mg + Trastuzumab in HER2 Enriched In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.	TRAS+CHEM±AI (HER2-Enriched) - Arm B Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Overall Study Disease progression (incl. death due to disease progression)	14	13	8
Overall Study Adverse Event	2	1	0
Overall Study Withdrawal by Subject	0	1	1
Overall Study Protocol Violation	1	0	0
Overall Study Investigator discretion	0	0	1

Baseline Characteristics

Evaluation of Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LAP+TRAS±AI (HER2-Enriched) - Arm A n=17 Participants Lapatinib 1000mg + Trastuzumab in HER2 Enriched In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=15 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C n=10 Participants Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.	Total n=42 Participants Total of all reporting groups
Age, Customized < 65 years	14 Participants n=5 Participants	15 Participants n=7 Participants	6 Participants n=5 Participants	35 Participants n=4 Participants
Age, Customized >= 65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	15 Participants n=7 Participants	10 Participants n=5 Participants	42 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	14 participants n=5 Participants	11 participants n=7 Participants	10 participants n=5 Participants	35 participants n=4 Participants
Race/Ethnicity, Customized African American	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: At screening and at disease progression, assessed up to approx. 3.5 years

Population: Evaluable Set: Included all subjects in Arm A who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=7 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Collectin subfamily member 12	0.51 Ratio of gene expression level Interval 0.151 to 0.794	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Complement C3b/C4b receptor 1 (Knops blood group)	0.51 Ratio of gene expression level Interval 0.227 to 0.901	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Membrane spanning 4-domains A1	0.25 Ratio of gene expression level Interval 0.078 to 0.589	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years POU class 2 associating factor 1	0.32 Ratio of gene expression level Interval 0.183 to 0.543	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD19+	0.35 Ratio of gene expression level Interval 0.106 to 0.904	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interleukin 6	0.36 Ratio of gene expression level Interval 0.033 to 0.832	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years G antigen 1	0.43 Ratio of gene expression level Interval 0.03 to 0.901	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years ubiquitin specific peptidase 9, Y-linked	0.50 Ratio of gene expression level Interval 0.321 to 0.77	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Thy-1 cell surface antigen	0.50 Ratio of gene expression level Interval 0.113 to 0.902	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Chemerin chemokine-like receptor 1	0.51 Ratio of gene expression level Interval 0.345 to 0.862	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Major histocompatibility complex, class II, DR beta 4	0.51 Ratio of gene expression level Interval 0.32 to 0.984	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD33 molecule	0.56 Ratio of gene expression level Interval 0.458 to 0.826	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years B-cell linker	0.56 Ratio of gene expression level Interval 0.326 to 0.874	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interleukin 12A	0.57 Ratio of gene expression level Interval 0.228 to 0.892	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD163+	0.57 Ratio of gene expression level Interval 0.417 to 0.911	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-C motif chemokine ligand 8	0.58 Ratio of gene expression level Interval 0.138 to 0.954	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Chemokine (C-C motif) receptor 1	0.59 Ratio of gene expression level Interval 0.501 to 0.792	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years POU class 2 homeobox 2	0.60 Ratio of gene expression level Interval 0.44 to 0.944	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Cyclin dependent kinase inhibitor 1A	0.62 Ratio of gene expression level Interval 0.453 to 0.873	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD27 molecule	0.62 Ratio of gene expression level Interval 0.357 to 0.886	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Lymphocyte antigen 86	0.63 Ratio of gene expression level Interval 0.383 to 0.906	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years TNF superfamily member 8	0.64 Ratio of gene expression level Interval 0.476 to 0.879	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD34+	0.67 Ratio of gene expression level Interval 0.558 to 0.863	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Integrin subunit alpha 6	0.68 Ratio of gene expression level Interval 0.47 to 0.827	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-type lectin domain containing 7A	0.69 Ratio of gene expression level Interval 0.326 to 0.944	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD180 molecule	0.70 Ratio of gene expression level Interval 0.347 to 0.869	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Integrin subunit alpha M	0.72 Ratio of gene expression level Interval 0.411 to 0.957	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Toll like receptor 6	0.72 Ratio of gene expression level Interval 0.511 to 0.836	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Autophagy related 10	0.73 Ratio of gene expression level Interval 0.662 to 0.864	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-C motif chemokine ligand 3 like 1	0.74 Ratio of gene expression level Interval 0.499 to 0.996	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Bone marrow stromal cell antigen 1	0.75 Ratio of gene expression level Interval 0.345 to 0.922	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD22+	0.76 Ratio of gene expression level Interval 0.629 to 0.936	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD37 molecule	0.76 Ratio of gene expression level Interval 0.553 to 0.884	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years NEG_A	0.77 Ratio of gene expression level Interval 0.674 to 0.949	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Sperm auto antigenic protein 17	0.79 Ratio of gene expression level Interval 0.697 to 0.968	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD200 molecule	0.79 Ratio of gene expression level Interval 0.598 to 0.945	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years TNF receptor associated factor 3	0.82 Ratio of gene expression level Interval 0.718 to 0.962	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interferon alpha and beta receptor subunit 1	1.10 Ratio of gene expression level Interval 1.036 to 1.124	—	—
Fold Change in Expression Profile of Genes and/or Proteins for Arm A (LAP+TRAS±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years TNF receptor associated factor 6	1.21 Ratio of gene expression level Interval 1.016 to 1.332	—	—

PRIMARY outcome

Timeframe: At screening and at disease progression, assessed up to approx. 3.5 years

Population: Evaluable Set: Included all subjects in Arm B who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=6 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Chemokine (C-C motif) receptor 1	0.52 Ratio of gene expression level Interval 0.159 to 0.815	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interleukin 24 gene	0.52 Ratio of gene expression level Interval 0.161 to 0.706	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Chemokine (C-X-C motif) receptor 2	0.53 Ratio of gene expression level Interval 0.295 to 0.629	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Strawberry notch homolog 2	1.13 Ratio of gene expression level Interval 1.045 to 1.3	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Zinc finger protein 205	1.42 Ratio of gene expression level Interval 1.144 to 1.815	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Fas associated via death domain	1.58 Ratio of gene expression level Interval 1.107 to 2.043	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD3e molecule associated protein	1.67 Ratio of gene expression level Interval 1.244 to 2.075	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Baculoviral IAP repeat containing 5	1.73 Ratio of gene expression level Interval 1.003 to 2.635	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interleukin 17 receptor B	2.01 Ratio of gene expression level Interval 1.151 to 2.975	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-type lectin domain containing 5A	0.16 Ratio of gene expression level Interval 0.02 to 0.44	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interferon induced transmembrane protein 1	0.25 Ratio of gene expression level Interval 0.183 to 0.421	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Fibronectin 1	0.27 Ratio of gene expression level Interval 0.077 to 0.393	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-C motif chemokine ligand 7	0.27 Ratio of gene expression level Interval -0.064 to 0.888	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Triggering receptor expressed on myeloid cells 1	0.27 Ratio of gene expression level Interval -0.018 to 0.959	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Plasminogen activator, urokinase	0.27 Ratio of gene expression level Interval 0.112 to 0.545	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interleukin 22 receptor subunit alpha 2	0.28 Ratio of gene expression level Interval 0.192 to 0.425	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-C motif chemokine ligand 8	0.28 Ratio of gene expression level Interval 0.044 to 0.699	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Tumor necrosis factor (ligand) superfamily member 4 gene	0.31 Ratio of gene expression level Interval 0.147 to 0.651	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Major histocompatibility complex, Class I-related	0.32 Ratio of gene expression level Interval 0.139 to 0.832	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Cathepsin L	0.32 Ratio of gene expression level Interval 0.066 to 0.82	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years SPP-1 (Osteopontin)	0.33 Ratio of gene expression level Interval 0.076 to 0.501	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Thy-1 cell surface antigen	0.34 Ratio of gene expression level Interval 0.157 to 0.648	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Transforming growth factor beta 2	0.35 Ratio of gene expression level Interval 0.12 to 0.504	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Hepatitis A virus cellular receptor 2	0.36 Ratio of gene expression level Interval 0.138 to 0.614	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Bone marrow stromal cell antigen 1	0.37 Ratio of gene expression level Interval 0.133 to 0.864	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-type lectin domain containing 7A	0.37 Ratio of gene expression level Interval 0.166 to 0.57	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years C-X-C motif chemokine ligand 5	0.38 Ratio of gene expression level Interval 0.04 to 0.943	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Collagen type III alpha 1 chain	0.40 Ratio of gene expression level Interval 0.13 to 0.685	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Complement C1s	0.41 Ratio of gene expression level Interval 0.088 to 0.717	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years IFIT1 gene	0.41 Ratio of gene expression level Interval 0.148 to 0.921	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Major histocompatibility complex, class I, G	0.41 Ratio of gene expression level Interval 0.147 to 0.698	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Tumour necrosis factor gene	0.42 Ratio of gene expression level Interval 0.108 to 0.945	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Integrin subunit beta 1	0.43 Ratio of gene expression level Interval 0.231 to 0.864	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Pro-melanin concentrating hormone	0.43 Ratio of gene expression level Interval 0.081 to 0.972	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD86+	0.44 Ratio of gene expression level Interval 0.102 to 0.7	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years FCGR3A SNP rs396991	0.44 Ratio of gene expression level Interval 0.107 to 0.696	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years TNF receptor superfamily member 10c	0.44 Ratio of gene expression level Interval 0.165 to 0.925	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Integrin subunit alpha M	0.45 Ratio of gene expression level Interval 0.166 to 0.797	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years TNF receptor superfamily member 11b	0.45 Ratio of gene expression level Interval 0.114 to 0.923	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Platelet derived growth factor C	0.45 Ratio of gene expression level Interval 0.231 to 0.797	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Mannan binding lectin serine peptidase 1	0.46 Ratio of gene expression level Interval 0.304 to 0.896	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Recombination activating 1	0.46 Ratio of gene expression level Interval 0.394 to 0.597	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interleukin 22	0.47 Ratio of gene expression level Interval 0.229 to 0.609	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Tumor necrosis factor (ligand) superfamily member 13b gene	0.47 Ratio of gene expression level Interval 0.179 to 0.697	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years BMI1 proto-oncogene, polycomb ring finger	0.47 Ratio of gene expression level Interval 0.322 to 0.735	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CXCL10 gene	0.48 Ratio of gene expression level Interval 0.074 to 0.986	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Leukocyte immunoglobulin like receptor B1	0.48 Ratio of gene expression level Interval 0.142 to 0.747	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years MX1 gene	0.48 Ratio of gene expression level Interval 0.155 to 0.781	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Tumor necrosis factor (ligand) superfamily member 11 gene	0.48 Ratio of gene expression level Interval 0.227 to 0.798	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Cathepsin S	0.49 Ratio of gene expression level Interval 0.138 to 0.807	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Interferon induced transmembrane protein 2	0.49 Ratio of gene expression level Interval 0.245 to 0.887	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years LYN proto-oncogene, Src family tyrosine kinase	0.50 Ratio of gene expression level Interval 0.36 to 0.685	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years Platelet derived growth factor receptor beta	0.50 Ratio of gene expression level Interval 0.16 to 0.801	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years OAS3 gene	0.50 Ratio of gene expression level Interval 0.284 to 0.899	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years CD58 molecule	0.50 Ratio of gene expression level Interval 0.398 to 0.619	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm B (TRAS+CHEM±AI (HER2-Enriched)) From Screening to Approx. 3.5 Years complement C3a receptor 1	0.51 Ratio of gene expression level Interval 0.147 to 0.949	—	—

PRIMARY outcome

Timeframe: At screening and at disease progression, assessed up to approx. 3.5 years

Population: Evaluable Set: Included all subjects in Arm C who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=7 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Fold Change in Expression Profile of Genes and /or Proteins for Arm C (Non-HER2- Enriched) From Screening to Approx. 3.5 Years Triggering receptor expressed on myeloid cells 1	0.50 Ratio of gene expression level Interval 0.294 to 0.995	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm C (Non-HER2- Enriched) From Screening to Approx. 3.5 Years Interleukin 1 receptor, type 1 gene	1.58 Ratio of gene expression level Interval 1.235 to 2.328	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm C (Non-HER2- Enriched) From Screening to Approx. 3.5 Years Complement component 2	2.13 Ratio of gene expression level Interval 1.011 to 3.567	—	—
Fold Change in Expression Profile of Genes and /or Proteins for Arm C (Non-HER2- Enriched) From Screening to Approx. 3.5 Years Coagulation factor XII	2.69 Ratio of gene expression level Interval 1.062 to 4.229	—	—

SECONDARY outcome

Timeframe: From randomization to disease progression or death, up to approx. 5.6 years

Population: Full Analysis Set (FAS): Consisted of all subjects who were randomized to study Arm A or Arm B or assigned to study Arm C, irrespective of whether they actually received study treatment.

PFS was defined as the time from the date of randomization (for Arm A and B) / treatment start date (for Arm C) to the date of the first documented disease progression or death due to any cause, whichever was earlier. If a subject had not progressed or died at the analysis cutoff date, PFS was censored at the time of the last adequate tumor assessment. PFS was summarized using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=17 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=15 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C n=10 Participants Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Progression-free Survival (PFS)	6.0 Months Interval 2.1 to 10.6	7.2 Months Interval 2.1 to 14.8	6.0 Months Interval 1.6 to 8.3

SECONDARY outcome

Timeframe: From enrollment/randomization to the end of study, approximately 5.6 years

Population: Full Analysis Set (FAS): Consisted of all subjects who were randomized to study Arm A or Arm B or assigned to study Arm C, irrespective of whether they actually received study treatment.

Overall response rate was defined as the percentage of subjects achieving either a confirmed complete response (CR) or partial response (PR) and was calculated from the Investigator's assessment of response per RECIST 1.1 criteria. . The confirmed CR or PR was derived using the following rules: confirmed CR - at least two determinations of CR at least 4 weeks apart before disease progression; confirmed PR - at least two determinations of PR or better at least 4 weeks apart before progression.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=17 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=15 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C n=10 Participants Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Overall Response Rate (ORR)	35.3 Percentage of participants Interval 14.2 to 61.7	33.3 Percentage of participants Interval 11.8 to 61.6	30.0 Percentage of participants Interval 6.7 to 65.3

SECONDARY outcome

Timeframe: From enrollment/randomization the end of study, approximately 5.6 years

Population: Full Analysis Set (FAS): Consisted of all subjects who were randomized to study Arm A or Arm B or assigned to study Arm C, irrespective of whether they actually received study treatment.

CBR is defined as percentage of subjects with a complete response (CR), partial response (PR), or maintaining stable disease (SD) for at least 24 weeks while on study according to the investigator assessment of response per RECIST 1.1 criteria. CR and PR are confirmed responses derived using the following rules: Confirmed CR - at least 2 determinations of CR at least 4 weeks apart before disease progression. Confirmed PR - at least 2 determinations of PR or better at least 4 weeks apart before progression.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=17 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=15 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C n=10 Participants Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Clinical Benefit Rate (CBR)	35.3 Percentage of participants Interval 14.2 to 61.7	46.7 Percentage of participants Interval 21.3 to 73.4	30.0 Percentage of participants Interval 6.7 to 65.3

SECONDARY outcome

Timeframe: From randomization to disease progression or death, up to approx. 5.6 years

Population: The number of patients with available biomarker data at both baseline and at progression is very small within each treatment arm (Arm A: n=7, Arm B: n=5, Arm C: n=5). This number of subjects is insufficient for an analysis to establish a relationship between the changes in biomarker at disease progression and progression free survival and would be statistically inappropriate to fit a model correlating changes in biomarkers with progression free survival with so few patients.

Describe if changes of biomarker expression at disease progression from baseline correlate with PFS.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: On-treatment deaths: up to approx. 168 weeks, Total deaths: up to approx. 5.6 years

Population: Clinical Database Population: All treated participants.

On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for Lapatinib, (treatment duration ranged from 151 to 164 weeks), 164 weeks for Trastuzumab (treatment duration ranged from 0 to 160 weeks), 168 weeks for Aromatase Inhibitors (treatment duration ranged from 9 to 164 weeks). Deaths post treatment survival follow up were collected after the on- treatment period, up to approx. 5.6 years.

Outcome measures

Outcome measures
Measure	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=17 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	TRAS+CHEM±AI (HER2-Enriched) - Arm B n=15 Participants Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2- Enriched - Arm C n=10 Participants Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
All-Collected Deaths Total Deaths	11 Participants	9 Participants	6 Participants
All-Collected Deaths On-treatment deaths	3 Participants	1 Participants	0 Participants

Adverse Events

LAP+TRAS±AI (HER2-Enriched) - Arm A

Serious events: 1 serious events

Other events: 15 other events

Deaths: 3 deaths

TRAS+CHEM±AI (HER2-Enriched) • ArmB

Serious events: 1 serious events

Other events: 14 other events

Deaths: 1 deaths

Non-HER2-Enriched - Arm C

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LAP+TRAS±AI (HER2-Enriched) - Arm A n=17 participants at risk Lapatinib 1000mg + Trastuzumab in HER2 Enriched In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.	TRAS+CHEM±AI (HER2-Enriched) • ArmB n=15 participants at risk Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.	Non-HER2-Enriched - Arm C n=10 participants at risk Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.
Cardiac disorders Cardiac arrest	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Escherichia sepsis	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Sepsis	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Urinary tract infection	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Hypoglycaemia	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Hypokalaemia	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Hypomagnesaemia	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Hyponatraemia	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Metabolic disorder	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.00% 0/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	6.7% 1/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Nervous system disorders Seizure	0.00% 0/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	10.0% 1/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	10.0% 1/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.9% 1/17 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/15 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/10 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 168 weeks for lapatinib, for a maximum duration of 164 weeks for trastuzumab and for a maximum duration of 168 weeks for aromatase inhibitors (anastrozole, letrozole and exemestane.) Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER