Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Hormones

Letrozole

Lapatinib

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Letrozole 2.5 mg administered orally fro 6 mos. plus placebo 1500 mg administered orally throughout the study until definitive surgery

Letrozole 2.5 mg administered orally fro 6 mos. plus lapatinib 1500 mg administered orally throughout the study until definitive surgery

lapatinib

letrozole

placebo

GSK Clinical Trials

Evaluate the percentage of clinical objective responses (cOR) in patients with HER2 negative early breast cancer treated with pre operative (neoadjuvant)lapatinib and letrozole

Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer

Letrozole Versus Letrozole Plus Lapatinib (GW572016) in Hormone-sensitive, HER-2 Negative Operable Breast Cancer. A Double Blind Randomized Phase II Study With Biomarker Evaluation.

cOR is defined as the documented evidence of complete response (CR) and partial response (PR) as assessed by ultrasound examination using Response Evaluation Criteria In Solid Tumors (RECIST). CR is defined as the disappearance of all target lesions (TLs) and non-TLs and the appearance of no new lesions (NLs). PR for TLs is defined as a \>=30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD. For non-TLs, it is defined as the persistence of \>=1 non-TL and no new TLs or non-TLs.

Complete clinical response=nodule not detectable; all ultrasound abnormalities detected at diagnosis have disappeared. Partial clinical response=the tumor's longest diameter (LD) is reduced by 50% or more; ultrasound characteristics of the tumor persist. Minimal response=the tumor's LD is reduced by 25%-49%. Stable disease=the tumor's LD is decreased by less than 25% and is increased by no more than 25% from the starting value. Progressive disease=the tumor's LD is increased by more than 25% from the starting value. Participants who were not evaluable did not have data available.

pCR is defined as the complete absence of infiltrating tumor cells (TCs) in the breast and lymph nodes. Miller and Payne criteria: Grade 1, no change/some alteration to individual malignant cells, but no reduction in overall cellularity; Grade 2, up to a 30% loss in TCs; Grade 3, between an estimated 30% and 90% reduction in TCs; Grade 4, more than a 90% reduction in TCs, only small cluster/dispersed cells remaining; Grade 5, no malignant identifiable cells; carcinoma in the milk ducts may be present. Grades 1 and 2 = No response; Grades 3 and 4= PR; Grade 5 = CR.

Tumors were categorized as follows: T0, no evidence of primary tumor, but carcinoma of the milk ducts, accumulation of abnormal cells in the breast lobules, or Paget disease (cancer condition that appears like a skin disease involving the breast nipple) with no associated tumor mass; T1, tumor was \<=2 centimeters (cm) across; T2, tumor was \>2 cm but \<5 cm across; T3, tumor was \>5 cm across; T4, tumor of any size growing into the chest wall or skin, including inflammatory breast cancer.

The nodal status of cancer indicates the involvement of lymph nodes in the participant with cancer. N0 indicates no involvement of lymph nodes, and N+ indicates involvement of lymph nodes.

Mastectomy is the medical term for the surgical removal of one or both breasts. Breast-conserving surgery (BCS) involves removing only the affected part of the breast tissue during surgery, as opposed to removal of the entire breast.

The percentage of participants who were planned to undergo a mastectomy at baseline but later underwent BCS was measured.

Toxicity was measured in grades (severity of the AE) as per National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI CTCAE) version (v) 3.0. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening/disabling; Grade 5, death related to the AE. Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, and hypertension is high blood pressure.

Cardiac safety was evaluated as any signs or symptoms of deterioration in LVEF. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was evaluated using NCI CTCAE.

Time to treatment failure is calculated as the interval between the date of randomization and the occurrence of local tumor progression (including ipsilateral \[on the same side\] and controlateral breast tumor progression), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional treatment arm), or death for any cause.

GlaxoSmithKline

Letrozole tablets in the dose of 2.5 milligrams (mg) plus matching placebo were administered orally once daily for 6 months prior to surgery.

Letrozole + Placebo

Letrozole tablets in the dose of 2.5 mg plus lapatinib ditosylate monohydrate tablets in the dose of 1500 mg were administered orally once daily for 6 months prior to surgery.

Letrozole + Lapatinib

Letrozole tablets in the dose of 2.5 mg plus lapatinib ditosylate monohydrate tablets in the dose of 1500 mg were administered orally once daily for 6 months prior to surgery

Total

Age, Continuous

Sex: Female, Male

GSK Response Center

Intent-to-Treat (ITT) Population: all participants who entered the study and received at least one dose of letrozole. Three participants withdrew consent and were not included in the efficacy analysis.

Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee

Complete Response

Partial Response

Minimal Response

Stable Disease

Progressive Disease

Not Evaluable

ITT Population. Three participants withdrew consent and were not included in the efficacy analysis.

Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria

Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria

ITT Population. Only those participants contributing data were analyzed.

Spots Global Cancer Trial Database for Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer

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Study Description

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