Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Letrozole

Estrogens

Progesterone

Antineoplastic Agents, Immunological

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Letrozole 2.5 mg tablets daily and Trastuzumab 2 mg/kg by IV weekly

Weekly trastuzumab (4 mg/kg loading dose given by IV over 90 minutes folowed by 2 mg/kg given by IV weekly over 30 minutes, provided the previous dose was well tolerated.

Paul K Marcom, MD

Matthew J Ellis, MB, PhD

The purpose of the study is to investigate the effects (good and bad) that the combination of the drugs letrozole (also called Femara™) and trastuzumab (also called Herceptin®) has on breast cancer. The United States (US) Food and Drug Administration has approved both letrozole and Herceptin for the treatment of advanced breast cancer. Doctors hope that the combination will work better than either drug alone.

Since ER function is regulated by peptide growth factor signaling, the phenotype of ER positive tumors may be influenced by the expression of growth factors and growth factor receptors. A potential interaction between ErbB2 (HER2/neu) expression and the success of endocrine therapy has been examined. ErbB2 expression was shown to correlate with resistance to hormone therapy.

An inverse relationship between endocrine therapy responsiveness and ErbB2 expression has not been observed in all studies. This may be due to discordant ER status between the primary tumor and metastatic sites. ER status can be discordant in approximately 20% of cases, with a tendency for metastatic disease to become ER negative with time. Data concerning ErbB2 is more limited, but there may be similar lack of concordance between primary tumor and metastases.

Inhibition of ErbB2 signaling may slow the development of resistance to estrogen deprivation therapy by inhibiting a pathway that promotes estrogen independent growth. The ErbB2 signal transduction pathway bypasses the requirement for estrogen for breast epithelial cell growth. When ErbB2 is activated in ER positive breast cancer cells in vitro, ER becomes phosphorylated and capable of stimulating transcription without estrogen. Chronic activation with heregulin, a ligand for the ErbB family of receptors, leads to ER down-regulation and the acquisition of an ER negative phenotype.

Estrogen deprivation therapy with selective aromatase inhibitors (SAIs) has become the standard of care for postmenopausal women with tamoxifen-resistant advanced breast cancer. About 1/3 of patients benefit from this therapy. There is interest in treating endocrine therapy refractory breast cancer with the recombinant DNA-derived humanized monoclonal antibody trastuzumab. When given alone, trastuzumab has an endocrine therapy-like risk benefit ratio. Trastuzumab targets ErbB2 (HER2/neu). Some breast cancers may coexpress ER and ErbB2.

Letrozole (Femara™) is a highly selective oral non-steroidal aromatase inhibitor. According to in vitro data, letrozole is 170-fold more potent in inhibiting aromatase than aminoglutethimide (AG) and 19-fold more active than anastrozole. Letrozole effectively inhibits intratumoral aromatase according to in vitro and in vivo data. It is indicated for the treatment of advanced breast carcinoma in post-menopausal women who have failed prior anti-estrogen therapy. Final FDA approval was granted in 1997. In two randomized phase IIb/III studies in patients previously treated with an antiestrogen, 19.5% and 23.6% of patients achieved an objective response with letrozole 2.5 mg/day compared with 12.4% receiving AG and 16.4% of patients receiving megace. Median overall survival was increased in the letrozole 2.5 mg/day group by 8 months compared to AG and by 3 months compared to megace. The lower 0.5 mg/day dose of letrozole was associated with poorer response rates and overall survival in both studies.

Trastuzumab (Herceptin®) was approved in 1998. A trial of trastuzumab as a single agent for first line treatment of advanced disease has been reported. Response rate in the first 62 patients was 24%.

The primary objective of this trial is to determine the proportion of patients with ER and/or PR positive, ErbB2 positive tamoxifen resistant metastatic breast cancer who achieve complete remission or partial remission or no significant change in lesion size for \> 24 weeks from a combination of letrozole and trastuzumab. The study will also determine duration of response and median time to progression, evaluate toxicity, generate a tumor and serum bank, and analyze ErbB2 expression on circulating malignant cells during treatment.

The study will enroll 35 patients

Letrozole, Herceptin in Her2neu +, Estrogen Receptor [ER] and/or Progesterone Receptor [PR] Positive, MBC

Phase II Trial of the Combination of Letrozole 2.5 mg Daily and Trastuzumab 2 mg/kg Weekly in ErbB2 Positive and Estrogen Receptor and/or Progesterone Receptor Positive Metastatic Breast Cancer

Genentech, Inc.

Novartis Pharmaceuticals

Duke University

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Mitogens

Lapatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Open Label - Combination Therapy (Lapatinib and Paclitaxel)

Lapatinib (GW572016) oral tablets

Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months

Paclitaxel infusion

Placebo

This was a randomized, double-blind, placebo-controlled, multicenter, Phase III study to evaluate and compare the efficacy and safety of Lapatinib + Paclitaxel versus Placebo + Paclitaxel in men and women with ErbB2 amplified metastatic (Stage IV) breast cancer who had not received prior therapy for metastatic disease.

Subjects were randomized to receive either Lapatinib (1500 mg once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks) or Placebo (once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks).

Subjects who progressed while on study and were on the placebo+paclitaxel arm were permitted to enter an extension phase of open label monotherapy therapy with lapatinib or open label combination therapy with lapatinib+paclitaxel and followed for response, progression and survival.

Based on the positive results in the primary analysis, Protocol Amendment 02 (dated 09 May 2011) discontinued further entry into the lapatinib monotherapy extension phase, and ongoing subjects taking placebo were permitted to replace it with open label lapatinib therapy (with or without continued paclitaxel therapy).

Following the primary Overall Survival (OS) analysis and subsequent implementation of Protocol Amendment 03, subjects who were still receiving active treatment entered the Long-term follow-up (LTFU) phase of the study. Reporting requirements in the LTFU phase were limited to Adverse events of special interest (AESI), Serious adverse events (SAEs) and pregnancy, and the subjects continued to receive treatment until the occurrence of unacceptable toxicity or disease progression (as determined by the investigator) or permanent withdrawal from treatment for any reason. Subjects who were no longer receiving active treatment were withdrawn from the study.

Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study of Lapatinib (GW572016) in Combination With Paclitaxel Versus Paclitaxel Plus Placebo in Subjects With ErbB2 Amplified Metastatic Breast Cancer

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause.

Progression-free survival (PFS) during the randomized phase was defined as the interval of time (in months) between the date of randomization and the earlier of date of disease progression (radiological or clinical assessment of symptomatic progression), or date of death due to any cause.

Overall response rate (ORR) during the randomized phase was evaluated per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and defined as the percentage of subjects achieving either a Complete Response (CR) or a Partial Response (PR). Participants with unknown or missing responses were treated as non-responders.

Clinical benefit rate (CBR) was defined as the percentage of subjects with evidence of CR or PR or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of \>=1 new lesions\], taking as reference the smallest sum LD since treatment start) of \>=24 weeks, based on confirmed responses from the investigator assessment of best overall response during the randomized phase.

For subjects who show CR or PR, duration of response (DOR) was defined to be the time from first documented evidence of PR or CR until the first documented sign of disease progression (radiological or clinical assessment of symptomatic progression) or death due to any cause, if sooner during the randomized phase.

The original outcome measure to be analyzed was Time to response (TTR) during the randomized phase defined as the time from randomization until first documented evidence of PR or CR (whichever status was recorded first); however, data were presented as the number of participants with a response at each nominal visit. Responses were based on the investigator's assessment, and only participants with a confirmed CR or PR were included in this analysis.

Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue.

Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression.

ORR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving either CR or PR. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue.

ORR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving either CR or PR. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. Tumors scored IHC 0/1+ were considered PTEN low.

CBR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving CR or PR or stable disease. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue.

CBR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving CR or PR or stable disease. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. Tumors scored IHC 0/1+ were considered PTEN low.

Any sign or symptom that occurs during the treatment period plus 30 days post-treatment. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.

Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m\^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks

Lapatinib 1500 mg + Paclitaxel

Matching placebo administered once daily plus paclitaxel 80 mg/m\^2 administered IV weekly for 3 weeks every 4 weeks

Placebo + Paclitaxel

Open Label - Monotherapy

Open Label - Combination Therapy

Total

Age, Continuous

Sex: Female, Male

White

Asian

Hispanic

Other

Race/Ethnicity, Customized

Metastasis is defined as the spread of a tumor or cancerous cells from the primary site to one or more sites elsewhere in the body. Visceral metastasis is defined as the spread of cancer to viscera, the internal organs of the body, specifically those within the chest (as the heart or lungs) or abdomen (as the liver, pancreas, or intestines). Non-visceral organs are defined as any organ not considered visceral.

Number of participants with any visceral metastatic disease and with only non-visceral disease

Cancer cells have hormone receptor expression of Estrogen Receptor (ER) and/or Progesterone Receptor (PR) and are thus considered to be ER+ and/or PgR+ cells, respectively.

Number of Participants with the Indicated Hormone Receptor Status

The stage of cancer is a description of the extent to which the cancer has spread. Stage I cancer is localized; Stage II cancer has not started to spread into the surrounding tissue, but the tumor is larger than in Stage I; Stage III cancer is locally advanced and/or involves local lymph nodes; Stage IV cancer has spread to other organs.

Number of Participants with the Indicated Stage of Disease at Initial Diagnosis

Eastern Cooperative Oncology Group (ECOG) Performance Status classifies participants according to their functional impairment, and scores indicate: 0, fully active; 1, ambulatory, restricted strenuous activity; 2, ambulatory, no work activity; 3, partially confined to bed; 4, totally confined in bed; 5, death. Participants were required to have a baseline ECOG performance status of 0 or 1 for study participation.

Number of Participants with the Indicated Eastern Cooperative Oncology Group Performance Status

Tumor cells move from the primary site to other sites in the body, where they continue to multiply and eventually form another clinically detectable tumor; thus, the site becomes metastatic. The table indicates number of metastatic sites.

Number of Participants with the Indicated Number of Metastatic Sites

The disease-free interval was defined as the time from initial diagnosis to metastases

Mean Time of Disease-Free Interval

The data collected for China patients after 01JUL2019 were excluded from analysis due to local regulations in China.

Study Director

Primary OS analysis cut-off date = 18-Jun-2010

Intent-to-Treat (ITT) Population. The ITT population was comprised of all randomized subjects and was based on the treatment to which the subject was randomized.

Overall Survival (OS) at 53 Months

Final OS analysis cut-0ff date = 23-Nov-2021

Overall Survival (OS) at 190 Months

Progression-free Survival (PFS) by Investigator Assessment

Overall Response Rate (ORR) by Investigator Assessment

Clinical Benefit Rate (CBR)

Subset of participants in the Intent-to-Treat (ITT) Population with a confirmed CR or PR

Duration of Response (DOR)

Week 8

Week 12

Week 16

Week 24

Week 32

Week 40

Week 48

Week 56

Week 64

Week 72

Participants in the Intent-to-Treat (ITT) Population with a confirmed CR or PR

Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72

Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PIK3CA mutations

Number of Tumors Evaluable for PIK3CA Mutations

Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PTEN

Number of Participants With Tumors Evaluable for PTEN

PIK3CA mutation

PIK3CA wild-type

Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PIK3CA mutations (PIK3CA mutation and PIK3CA wild type)

Predictive Effect of PIK3CA Mutations Status on Overall Response Rate (ORR)

PTEN low

Without PTEN low

Participants in the Intent-to-Treat (ITT) Population with PTEN low and without PTEN low

Predictive Effect of PTEN Low on Overall Response Rate (ORR)

Predictive Effect of PIK3CA Mutations Status on Clinical Benefit Rate (CBR)

Predictive Effect of PTEN Low on Clinical Benefit Rate (CBR)

Randomized Phase

Open Label Phase

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

750 mg lapatinib administered orally twice daily

lapatinib

Determine how safe and effective lapatinib is when used to treat patients with ErbB2 overexpressing breast cancer that has spread to the brain and is still progressing there even after radiation treatment using WBRT (whole brain radiotherapy) or SRS (stereotactic radiosurgery) to the brain. Lapatinib is an oral drug that will be taken every day. Tests for safety and efficacy will be performed every 4 weeks or 8 weeks (depending on the test) during the course of the study.

Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer

A Phase II Study of Lapatinib for Brain Metastases in Subjects With ErbB2-Positive Breast Cancer Following Trastuzumab-based Systemic Therapy and Cranial Radiotherapy

Summary of CNS Objective Response (Lapatinib Monotherapy - MITT Population)

Response to lapatinib in patients with progressive brain metastases from ErbB2-overexpressing breast cancer.

The primary indicator of drug efficacy was CNS objective response rate. A CNS objective response was defined as either a Complete response (CR) or Partial response (PR), as assessed by volumetric analysis of brain Magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of Neurological signs and symptoms (NSS)

A CNS objective response rate was defined as a 50% volumetric reduction in sum of CNS target lesions, with no new or progressive CNS or non-CNS lesions, no increases in tumor-related steroid requirements and no worsening of neurological signs or symptoms

Summary of CNS Objective Response (the Complete Response + Partial Response)

Physician-reported NSS worksheet is derived from 13 AEs and measured by NCI CTCAE v3.0 grouped into 7 categories: level of consciousness, neurological symptoms, cranial nerves, language, strength, sensation, \& ataxia. Improvement of NSS required: Decrease by 1 or more grades from baseline of any tumor-related NSS, with confirmation at least 4 wks later, No development or worsening in any tumor-related NSS during interval, No radiographic evidence of CNS progression (assessed by volumetric MRI) or systemic (non-CNS) progression (assessed by RECIST) during interval, Stable or decreasing steroids during interval as defined by GSK equivalent doses of an alternative corticosteroid or a dose increase for non-tumor related reasons didn't constitute a steroid increase. Improvement in any non-tumor associated NSS didn't constitute improvement in NSS. Neurological exam, using Neurological Examination Worksheet was assessed at baseline \& each 4 wks. Categories below are not mutually exclusive.

Summary of Proportion of Subjects with a CNS Objective Response or Improvement in Baseline NSS

The duration of CNS objective response, defined as the time from first CNS

Objective response until tumor progression at any site or death due to any cause.

A CNS objective response was defined as either a Complete Response (CR) or Partial Response (PR), as assessed by volumetric analysis of magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of tumor-related neurological signs or symptoms.

The CNS disease control rate, defined as the percentage of subjects with CR, PR or stable disease at Week 24

Summary of Kaplan-Meier Estimates for Progression Free Survival at Any Site

Overall survival (OS) defined as the time from initiation of investigational product to death due to any cause.

baseline to time of disease progression or death

Summary of Overall All-cause mortality (Main Study and Extension)

All cause mortality (on-treatment deaths) was collected for as long as participants could be contacted from FPFV until LPLV up to a maximum of 12 years and 3 months

SAEs are presented from main and extension phase

Cohort A subjects had Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and one or two prior trastuzumab-containing regimens, in total, for treatment of breast cancer in adjuvant and/or metastatic settings

EGF105084/Cohort A

Cohort B subjects had ECOG performance status 2 and/or more than 2 prior trastuzumab-containing regimens for treatment of breast cancer in the adjuvant and/or metastatic settings

EGF105084/Cohort B

Overall - Main Study and Extension Phase - 750 mg lapatinib administered orally twice daily Cohort A subjects had Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and one or two prior trastuzumab-containing regimens, in total, for treatment of breast cancer in adjuvant and/or metastatic settings.

Cohorts A

750mg lapatinib administered orally twice daily. Cohort B subjects had ECOG performance status 2 and/or more than 2 prior trastuzumab-containing regimens for treatment of breast cancer in the adjuvant and/or metastatic settings.

Cohort B

<18 years

18-64 years

65-84 years

>85 years

Age, Customized

African American/African

American Indian/Alaskan Native

Asian - Central/South

Asian - Japanese

Asian - South-East Asian

Asia - East

Native Hawaiian or other Pacific Islander

White - Arabic/North African

White - White/ Caucasian/European

Mixed race

Unknown

Intent-to-Treat (ITT) Population is defined as all subjects who received at least one dose of study medication.

Outcome Quantitative Toxicities Associated with Oral Lapatinib are in Adverse Events section. No analysis was performed for 2 outcomes: Relationship of PET Uptake, as Predictors of Response; and Relationship Between Genetic Variants in Select Genes

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Progressive disease (PD)

750mg lapatinib administered orally twice daily. Cohort A subjects had Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and one or two prior trastuzumab-containing regimens, in total, for treatment of breast cancer in adjuvant and/or metastatic settings

Cohort A

Modified ITT (MITT) Population is defined as all subjects who received at least four doses (750 mg lapatinib 2x daily for 2 days) of study medication and who had measurable brain metastases (greater than or equal to 1cm in diameter) at baseline assessment. MITT was the primary population for analysis of efficacy data in lapatinib monotherapy arm.

The Number of Participants With Central Nervous System (CNS) Best Overall Response

The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)

Subjects with NSS improvement

>=20% volumetric reduction of lesion

any volumetric reduction of lesion

volumetric increase or withdrew

Overall - Main Study and Extension Phase - 750 mg lapatinib administered orally twice daily

Cohorts A and B

MITT population

Analysis was performed on combined cohorts in order to have a sufficient sample size to analyze association of CNS Volumetric Change from Baseline and NSS Improvement

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Letrozole, Herceptin in Her2neu +, Estrogen Receptor [ER] and/or Progesterone Receptor [PR] Positive, MBC	NCT00134680	Metastatic Brea...	Letrozole Trastuzumab	18 Years -	Duke University
Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2	NCT00281658	Neoplasms, Brea...	Lapatinib (GW57... Paclitaxel infu... Placebo	18 Years -	Novartis
Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer	NCT00263588	Neoplasms, Brea...	lapatinib	18 Years -	Novartis
Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.	NCT00524303	Neoplasms, Brea...	Trastuzumab Paclitaxel FEC75 Lapatinib	18 Years -	GlaxoSmithKline
Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2	NCT00281658	Neoplasms, Brea...	Lapatinib (GW57... Paclitaxel infu... Placebo	18 Years -	Novartis
Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.	NCT00524303	Neoplasms, Brea...	Trastuzumab Paclitaxel FEC75 Lapatinib	18 Years -	GlaxoSmithKline
EAP (Expanded Access Protocol) Of Lapatinib Combined With Capecitabine In Metastatic Breast Cancer	NCT00338247	Neoplasms, Brea...	lapatinib + cap...	18 Years -	Novartis

Spots Global Cancer Trial Database for erbb2 positive