Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Amino Acids

Paclitaxel

Trastuzumab

Cyclophosphamide

Fluorouracil

Albumin-Bound Paclitaxel

Epirubicin

Lapatinib

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Trastuzumab alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles and Paclitaxel for 4 (21 day) cycles then continued trastuzumab until time of definitive surgery

Lapatinib alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued lapatinib until time of definitive surgery

Trastuzumab + Lapatinib for 2 weeks then added FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued trastuzumab + lapatinib until time of definitive surgery

4mg/kg IV loading dose followed by 2mg/kg IV weekly

5FU 500mg/m2 + Epirubicin 75 mg/m2 + cyclophosphamide 500 mg/m2 IV on day 1 of 4 (21 day) cycles

FEC75

1250 mg oral daily dose in arm 2, 750 mg oral daily dose for FEC cycles and then 1000 mg oral daily dose during the Paclitaxel cycles in arm 3

GSK Clinical Trials

This study will examine safety and efficacy of Lapatinib in combination with a standard neoadjuvant chemotherapy including 5FU, Epirubicin, Cyclophosphamide and Paclitaxel. Tumor tissue will be obtained at 3 timepoints (optional 4th) to evaluate tumor response to treatment.

Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.

Phase II Randomized Trial of Neoadjuvant Trastuzumab and/or Lapatinib Plus Chemotherapy (Sequential FEC75 and Paclitaxel) in Women With ErbB2- (HER2/Neu-) Overexpressing Invasive Breast Cancer

Expression (exp) of biomarker proteins (prot) were analyzed to determine if individual prot levels either in the Baseline or Day 14 breast tumor biopsy specimen correlated with breast pCR. A biomarker indicates a change in exp or state of a prot that correlates with the risk or disease progression, or with the susceptibility of the disease to a given treatment. Biomarkers are characteristic biological properties that can be detected and measured in parts of the body like blood or tissue. pCR=yes: participants (par.) had breast pCR. pCR=no: par. did not have breast pCR. Prot exp values are represented as normalized, scaled values; the unit of measurement is unit-less. Raw exp values were processed as follows: background subtraction of the raw exp value, then that value divided by beta-acting exp to normalize the exp value. A Standard Z score was calculated to scale the exp value.

Stem cell data were of poor quality and thus could not be analyzed. Increases or decreases in cancer stem cells and how the changes correlated with response/non-response to treatment were to have been assessed.

Transcriptional data were of poor quality and thus could not be analyzed. Gene pathways that correlate with response/non-response to treatment were to have been evaluated. The unit of measure is unit less; however, the processed values would be considered normalized relative expression level.

A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ \[DCIS\] or lobular carcinoma in situ \[LCIS\] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.

cCR was defined as the percentage of participants achieving either a Complete Response (CR) or a Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Percentage is the Kaplan Meier estimate of DFS. DFS is time from randomization until disease recurrence (contralateral breast cancer; second primary cancer; progression during neo-adjuvant treatment; or death from any cause). Par. who experienced progression during treatment and were withdrawn were considered to have a DFS event at withdrawal.

12-lead ECGs were performed, and participants were classified as having normal ECG, abnormal- not clinically significant (NCS) ECG, and abnormal-clinically significant (CS) ECG per investigator opinion and reported result.

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 and is used to determine cardiac function. LVEF was measured by performing echocardiogram (ECHO). If ECHO could not be performed or if the investigator believed that it was not conclusive to evaluate LVEF, then a multigated acquisition (MUGA) scan was performed.

GlaxoSmithKline

In the Safety Population, serious and non-serious adverse events were collected from all randomized participants who received at least one dose of investigational product and was based on the actual treatment received if this differed from that to which the participant was randomized.

Participants received trastuzumab alone (a loading dose of 4 milligrams \[mg\]/kilogram \[kg\] on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter). Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil \[5-FU\] 500 mg/meters squared \[m\^2\], epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m\^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.

Participants received lapatinib alone (1250 mg orally \[PO\] once daily \[QD\]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m\^2, epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m\^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.

Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m\^2, epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 x 4 cycles on Day 1), then paclitaxel (80 mg/m\^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.

Trastuzumab+Lapatinib

Total

Age, Continuous

Sex: Female, Male

African American/African heritage

American Indian or Alaska native

Asian - Central/South Asian heritage

Asian - East Asian heritage

Asian - South East Asian heritage

White - Arabic/North African heritage

White - White/Caucasian/European heritage

Mixed race

Race/Ethnicity, Customized

GSK Response Center

Intent-to-Treat-Evaluable (ITT-E) Population: ITT participants with evaluable tumor responses who had been \>=75% compliant to 5-fluorouracil (5-FU) 500 mg/m\^2, epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 (FEC75) and paclitaxel 80 mg/m\^2 and had undergone surgery.

Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy

ITT Population: all randomized participants regardless of whether they had received any treatment.

Percentage of Participants With Clinical Complete Response (cCR) at 26 Weeks or at End of Treatment (EOT) or Early Withdrawal

Percentage of Participants (Par.) With Disease-free Survival (DFS) at the End of 5 Years From Randomization

Baseline, Normal, n= 28, 32, 30

Baseline, Abnormal-NCS, n= 28, 32, 30

Baseline, Abnormal-CS, n= 28, 32, 30

EOT/early withdrawal, Normal, n= 16, 21, 16

EOT/early withdrawal, Abnormal-NCS, n= 16, 21, 16

EOT/early withdrawal, Abnormal-CS, n= 16, 21, 16

Safety Population: all randomized participants (par) who received at least one dose of investigational product, based on actual treatment received if this differed from that to which par was randomized. Not all par were analyzed: some par were randomized to an arm they did not want or par were randomized in error (eligibility criteria weren't met).

Number of Participants With the Indicated Electrocardiogram (ECG) Status at Baseline and at EOT or Early Withdrawal

Week 3, n= 30, 31, 26

Week 9, n= 30, 32, 27

Week 15, n= 31, 34, 28

Early withdrawal/EOT, n= 31, 34, 28

3-month survival follow-up, n= 31, 34, 28

6-month survival follow-up, n= 31, 34, 28

Participants received trastuzumab alone (a loading dose of 4 milligrams (mg)/kilogram (kg) on Day 1, followed by a dose of 2 mg/kg on Day 1 of Week 2 and weekly thereafter. Participants were treated with trastuzumab in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-fluorouracil \[5-FU\] 500 mg/meters squared \[m\^2\], epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 x 4 cycles on Day 1), then paclitaxel 80 mg/m\^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab.

Participants received lapatinib alone (1250 mg orally \[PO\] once daily \[QD\]). Participants were treated with lapatinib in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m\^2, epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 x 4 cycles on Day 1), then paclitaxel 80 mg/m\^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with lapatinib.

Participants received trastuzumab (given as in Arm 1) and lapatinib (750/1000 mg PO QD). Participants were treated with these medications in a 2-week run-in period. On Day 14, a second core needle biopsy was performed, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each (1 cycle=3 weeks): FEC75 (5-FU 500 mg/m\^2, epirubicin 75 mg/m\^2, cyclophosphamide 500 mg/m\^2 x 4 cycles on Day 1), then paclitaxel 80 mg/m\^2 x 4 cycles on Day 1, Day 8, and Day 15) in combination with trastuzumab+lapatinib.

Safety Population. Not all participants in the Safety Population were analyzed: some participants were randomized to an arm they did not want or participants were randomized in error (eligibility criteria weren't met).

Cumulative Number of Participants With at Least One Decrease of More Than or Equal to 20% in Left Ventricular Ejection Fraction (LVEF) at the Indicated Time Points Compared to LVEF at Baseline

Baseline, EGFR_Tyr1068; pCR=yes, n=0, 4

Baseline, Baseline, EGFR_Tyr1068; pCR=no, n=0, 11

Post Baseline, EGFR_Tyr1068; pCR=yes, n=9, 0

Post Baseline, EGFR_Tyr1068; pCR=no, n=6, 0

Day 14, pSTAT5; pCR=yes, n=11, 6

Day 14, pSTAT5; pCR=no, n=9, 11

Post Baseline, PI3K; pCR=yes, n=0, 5

Post Baseline, PI3K; pCR=no, n=0, 10

Post Baseline, LC3B; pCR=yes, n=0, 5

Post Baseline, LC3B; pCR=no, n=0, 10

Post Baseline, MMP9; pCR=yes, n=0, 5

Post Baseline, MMP9; pCR=no, n=0, 5

Post Baseline, GSK3_a_b_Tyr279_216; pCR=yes, n=8,0

Post Baseline, GSK3_a_b_Tyr279_216; pCR=no, n=5,0

ITT-E Population. Only those participants with matched pairs of biopsy samples for analysis at Baseline and on Day 14 were analyzed.

Spots Global Cancer Trial Database for Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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