Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Trastuzumab

Immunoglobulins

Lapatinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Endocrine

Mothaffar Rimawi, MD

We think that lapatinib will help to shrink your tumor when given prior to the main or primary therapy for the kind of breast cancer you have been diagnosed with. When treatment is given before the main or primary therapy, it is called neoadjuvant therapy. We will compare lapatinib with lapatinib plus trastuzumab (herceptin) for 12 weeks. If your tumor is estrogen receptor positive (ER positive), estrogen deprivation will also be given to you. Tumors that are ER positive have a lot of estrogen receptors found in them. This is also called "over expression" or amplification of estrogen receptors.

The most important information we will get from this study is to see the response to "neoadjuvant" (treatment given before the main treatment), lapatinib with trastuzumab (herceptin) in your tumor tissue sample.

The neoadjuvant setting is especially attractive for studies of predictive biologic correlates for several reasons including early assessment of response to therapy, access to the primary tumor, and reduced patient numbers compared to those required in the adjuvant setting. Response to neoadjuvant therapy is a validated surrogate marker for improved survival; it may be used to test the overall efficacy of neoadjuvant treatment regimens and response in the primary tumor mirrors the effect of therapy on micrometastases.

Trastuzumab is an efficacious agent in HER2 overexpressing breast cancers. Our results with neoadjuvant trastuzumab indicate that its efficacy may be better in patients with treatment-naïve tumors compared to metastatic disease, with 26% of patients showing a partial response after only 3 weeks of therapy. No patients progressed during this 3-week period. We have also conducted a neoadjuvant lapatinib study given as a single agent for 6 weeks. The response rates in this second study have been impressive with greater than 80% responses in patients with HER2 positive locally advanced breast cancers. It is likely that the true response rate to HER2 blockade would be higher had therapy been continued for longer. We therefore hypothesize that lapatinib, a dual tyrosine kinase inhibitor, together with trastuzumab, will result in tumor regression when given as neoadjuvant therapy in HER2 overexpressing breast cancer. We will compare lapatinib plus trastuzumab for 12 weeks, and if the tumors express ER, estrogen deprivation will also be administered.

This is a phase II trial. Clinical efficacy will be assessed by bidimensional tumor measurements of the primary cancer at baseline, and at the end of week 12. Objective tumor response rate defined as objective bidimensional tumor measurements after neoadjuvant treatment at 12 weeks will be calculated, and assessed according to standard RECIST criteria. Pathologic responses will be graded as pathologic complete response if there is no invasive cancer in the residual breast at the time of surgery. Near pathologic complete response will also be documented as residual disease of less than 1 cm.

Lapatinib and Trastuzumab With or Without Endocrine Therapy

A Phase II Trial of Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2 Overexpressing Breast Cancer Patients

Pathologic Assessment After 12 weeks of lapatinib and trastuzumab with or without endocrine therapy. Pathologic complete response: no invasive cancer in the residual breast. Near pathologic complete response: residual disease of less than 1 cm in breast.

GlaxoSmithKline

Baylor Breast Care Center

Medical Director

All study participants received lapatinib 1000mg daily and trastuzumab 4mg/kg loading dose and then 2mg/kg every week

Lapatinib + Trastuzumab

Age, Continuous

Sex: Female, Male

Dr. Mothaffar Rimawi

Complete Pathologic Response

Near Complete Pathologic Response

Not Pathologic response

All study participants received lapatinib 1000mg daily and trauzumab 4mg/kg loading dose and then 2mg/kg every week

65 patients were enrolled and received the study treatment. 1 patient was found ineligible for this study therefore she was excluded from outcome report.

Pathologic Assessment After Study Treatment

Data Analysis of the Biomarkers: Immunohistochemical Staining of Cells From Breast Biopsies and Skin Biopsies Will be Performed.

All study participants received lapatinib 1000mg daily and Trastuzumab 4mg/kg loading dose and then 2mg/kg every week

Overall Study

Spots Global Cancer Trial Database for locally advanced breast cancers