Trial Outcomes & Findings for Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy (NCT NCT00999804)

Last Updated: 2025-03-12

Results Overview

Pathologic complete response was defined as no residual invasive cancer in the breast, after 12 or 24 weeks of lapatinib/trastuzumab with or without endocrine therapy. This outcome is based on patient's pathological report. We are not measuring the clinical response. Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

128 participants

Primary outcome timeframe

12 or 24 week depending the arm assignment

Results posted on

2025-03-12

Participant Flow

Participants were recruited between October 2011 and July 2014 at 10 study sites: Baylor College of Medicine, UAB, University of Chicago, Johns Hopkins, Duke, Indiana University, Vanderbilt, MDACC, DFCI, and Mayo Clinic.

Participants screened up to 28-day period.

Participant milestones

Participant milestones
Measure	24-week Arm Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Overall Study STARTED	85	43
Overall Study COMPLETED	64	38
Overall Study NOT COMPLETED	21	5

Reasons for withdrawal

Reasons for withdrawal
Measure	24-week Arm Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Overall Study Lack of Efficacy	9	2
Overall Study Adverse Event	4	3
Overall Study Withdrawal by Subject	4	0
Overall Study Death	1	0
Overall Study Ineligible	3	0

Baseline Characteristics

Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	24-week Arm n=85 Participants Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 Participants Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Total n=128 Participants Total of all reporting groups
Age, Continuous	50 years n=5 Participants	57 years n=7 Participants	52 years n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	43 Participants n=7 Participants	128 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=5 Participants	33 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) White	68 Participants n=5 Participants	31 Participants n=7 Participants	99 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 or 24 week depending the arm assignment

Population: Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participant were not evaluable: 3 participant were found ineligible for the study and one participant died before surgery.

Outcome measures

Outcome measures
Measure	24-week Arm n=81 Participants Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 Participants Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Pathologic Complete Response pathologic complete response	20 participants	5 participants
Pathologic Complete Response non-complete pathologic response	61 participants	38 participants

SECONDARY outcome

Timeframe: 12 week or 24 weeks depending on arm assignment

Population: Participants who started the study treatment will be evaluable for safety analysis

the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy

Outcome measures

Outcome measures
Measure	24-week Arm n=85 Participants Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 Participants Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Number of Participants With Adverse Events	61 participants	26 participants

SECONDARY outcome

Timeframe: 12 weeks or 24 weeks depending on arm assignment

pathologic complete response was defined as no residual invasive cancer in the breast and the axillary lymph nodes.

Outcome measures

Outcome measures
Measure	24-week Arm n=81 Participants Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 Participants Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Total Pathologic Complete Response total complete pathologic response	8 participants	2 participants
Total Pathologic Complete Response not total complete pathologic response	72 participants	41 participants

SECONDARY outcome

Timeframe: 12 weeks or 24 weeks depending on arm assignment

Outcome measures

Outcome measures
Measure	24-week Arm n=81 Participants Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 Participants Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Clinical Response Complete response	46 participants	21 participants
Clinical Response Partial response	10 participants	13 participants
Clinical Response Stable disease	2 participants	3 participants
Clinical Response Progressive disease	13 participants	4 participants
Clinical Response Unknown	10 participants	2 participants

Adverse Events

24-week Arm

Serious events: 3 serious events

Other events: 61 other events

Deaths: 0 deaths

12-week Arm

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	24-week Arm n=85 participants at risk Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 participants at risk Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Cardiac disorders Cardiac arrest	1.2% 1/85 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	0.00% 0/43 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Hepatobiliary disorders Elevated AST	1.2% 1/85 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	0.00% 0/43 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Infections and infestations Breast infection	1.2% 1/85 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	0.00% 0/43 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Renal and urinary disorders Acute kidney injury	0.00% 0/85 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	2.3% 1/43 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Renal and urinary disorders Hematuria	0.00% 0/85 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	2.3% 1/43 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Renal and urinary disorders Renal calculi	0.00% 0/85 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	2.3% 1/43 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Renal and urinary disorders Urinary retention	0.00% 0/85 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	2.3% 1/43 • Number of events 1 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.

Other adverse events

Additional Information

Dr. Mothaffar Rimawi

Baylor College of Medicine

Phone: 7137981311

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	24-week Arm n=85 participants at risk Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	12-week Arm n=43 participants at risk Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Investigations Alanine aminotransferase increased	25.9% 22/85 • Number of events 54 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	11.6% 5/43 • Number of events 7 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Investigations Alkaline phosphatase increased	14.1% 12/85 • Number of events 17 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	7.0% 3/43 • Number of events 3 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Skin and subcutaneous tissue disorders Alopecia	3.5% 3/85 • Number of events 3 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	9.3% 4/43 • Number of events 4 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Blood and lymphatic system disorders Anemia	9.4% 8/85 • Number of events 16 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	9.3% 4/43 • Number of events 11 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Metabolism and nutrition disorders Anorexia	9.4% 8/85 • Number of events 10 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	7.0% 3/43 • Number of events 3 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Psychiatric disorders Anxiety	4.7% 4/85 • Number of events 4 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	7.0% 3/43 • Number of events 3 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Investigations Aspartate aminotransferase increased	27.1% 23/85 • Number of events 46 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	16.3% 7/43 • Number of events 7 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Investigations Blood bilirubin increased	9.4% 8/85 • Number of events 15 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	0.00% 0/43 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Gastrointestinal disorders Diarrhea	35.3% 30/85 • Number of events 51 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	32.6% 14/43 • Number of events 22 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Skin and subcutaneous tissue disorders Dry skin	9.4% 8/85 • Number of events 9 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	4.7% 2/43 • Number of events 2 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Nervous system disorders Dysgeusia	4.7% 4/85 • Number of events 4 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	9.3% 4/43 • Number of events 4 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
General disorders Fatigue	16.5% 14/85 • Number of events 19 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	18.6% 8/43 • Number of events 8 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Nervous system disorders Headache	5.9% 5/85 • Number of events 5 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	4.7% 2/43 • Number of events 2 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Vascular disorders Hot flashes	9.4% 8/85 • Number of events 8 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	9.3% 4/43 • Number of events 4 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Psychiatric disorders Insomnia	8.2% 7/85 • Number of events 7 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	9.3% 4/43 • Number of events 4 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Gastrointestinal disorders Mucositis oral	10.6% 9/85 • Number of events 15 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	23.3% 10/43 • Number of events 10 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
General disorders Nusea	12.9% 11/85 • Number of events 15 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	14.0% 6/43 • Number of events 6 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
General disorders Pain	5.9% 5/85 • Number of events 6 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	4.7% 2/43 • Number of events 2 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	5.9% 5/85 • Number of events 5 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	7.0% 3/43 • Number of events 3 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Skin and subcutaneous tissue disorders Rash acneiform	20.0% 17/85 • Number of events 22 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	11.6% 5/43 • Number of events 5 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Gastrointestinal disorders Vomiting	7.1% 6/85 • Number of events 11 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.	4.7% 2/43 • Number of events 2 • 7 months Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.