Trial Outcomes & Findings for Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer (NCT NCT01273610)

Last Updated: 2025-06-10

Results Overview

Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to lapatinib or trastuzumab.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Until 30 days after last dose of treatment, an average of 8 months

Results posted on

2025-06-10

Participant Flow

Participant milestones

Participant milestones
Measure	Age <=75 Patients receive lapatinib ditosylate PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lapatinib: 250 mg tablets Trastuzumab: Intravenous injection laboratory biomarker analysis pharmacological study	Age >75 Patients receive lapatinib ditosylate PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lapatinib: 250 mg tablets Trastuzumab: Intravenous injection laboratory biomarker analysis pharmacological study
Overall Study STARTED	30	10
Overall Study COMPLETED	30	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Age ≤75 n=30 Participants Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age >75 n=10 Participants Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=40 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	84 years n=7 Participants	72 years n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	9 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants	9 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	6 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	10 participants n=7 Participants	40 participants n=5 Participants
ECOG performance status Fully active, able to carry on all pre-disease performance without restriction	19 Participants n=5 Participants	4 Participants n=7 Participants	23 Participants n=5 Participants
ECOG performance status Restricted in physically strenuous activity but ambulatory and able to do work of a light nature	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
ECOG performance status Ambulatory and capable of selfcare but unable to do work activities; up and about >50% waking hours	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Until 30 days after last dose of treatment, an average of 8 months

Outcome measures

Outcome measures
Measure	Age ≤75 n=30 Participants Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age >75 n=10 Participants Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Percent of Participants With Grade 3 or Higher Non-hematological Toxicities and Symptomatic Congestive Heart Failure	17 percentage of participants Interval 6.0 to 35.0	30 percentage of participants Interval 7.0 to 65.0

SECONDARY outcome

Timeframe: While on treatment, up to 4.5 years

Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated. A dose modification was defined as a hold (participant started the dose later than scheduled), reduction (subject was given a lower dose than originally scheduled), or discontinuation (subject stopped treatment) of lapatinib.

Outcome measures

Outcome measures
Measure	Age ≤75 n=30 Participants Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age >75 n=10 Participants Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Percent of Participants With a Dose Modifications	37 percentage of participants Interval 20.0 to 56.0	60 percentage of participants Interval 26.0 to 88.0

SECONDARY outcome

Timeframe: While on treatment, up to 4.5 years

RECIST: Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): 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 (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Age ≤75 n=30 Participants Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age >75 n=10 Participants Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Complete response (CR)	0 Participants	1 Participants
Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Partial response (PR)	7 Participants	1 Participants
Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Stable Disease (SD)	6 Participants	3 Participants
Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Progressive Disease	12 Participants	0 Participants
Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Not evaluable	5 Participants	5 Participants

SECONDARY outcome

Timeframe: From the date treatment begins until the first date on which recurrence, progression or death due to any cause, with an average follow up of 1 year.

Median PFS and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated across all ages per protocol plan. Progression is defined using RECIST v1.0, as 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 (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Age ≤75 n=40 Participants Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age >75 Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Median Progression-free Survival (PFS)	2.7 months Interval 2.5 to 12.0	—

SECONDARY outcome

Timeframe: Time from start of treatment to death due to any cause, with average follow up of 4.5 years

OS will be estimated using the product limit method of Kaplan and Meier across all ages per protocol plan.

Outcome measures

Outcome measures
Measure	Age ≤75 n=40 Participants Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age >75 Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Median Overall Survival (OS)	30.8 months Interval 17.9 to 39.9	—

Adverse Events

Age ≤75

Serious events: 8 serious events

Other events: 30 other events

Deaths: 19 deaths

Age > 75

Serious events: 6 serious events

Other events: 9 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Daneng Li

City of Hope

Phone: 626-359-8111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Age ≤75 n=30 participants at risk Participants 75 years of age and under receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Age > 75 n=10 participants at risk Participants over 75 years of age receive lapatinib ditosylate 250mg PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Diarrhea	10.0% 3/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Gastrointestinal disorders Nausea	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Gastrointestinal disorders Vomiting	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Infections and infestations Bladder infection	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Infections and infestations Lung infection	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Metabolism and nutrition disorders Dehydration	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Metabolism and nutrition disorders Hyperglycemia	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Metabolism and nutrition disorders Hypoglycemia	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Metabolism and nutrition disorders Hypokalemia	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Metabolism and nutrition disorders Hyponatremia	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Nervous system disorders Dizziness	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Nervous system disorders Edema cerebral	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Nervous system disorders Presyncope	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Nervous system disorders Seizure	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Nervous system disorders Vasovagal reaction	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Psychiatric disorders Anxiety	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Psychiatric disorders Confusion	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Psychiatric disorders Psychosis	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	10.0% 1/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years
Skin and subcutaneous tissue disorders Rash maculo-papular	3.3% 1/30 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years	0.00% 0/10 • On treatment plus 30 days following discontinuation of treatment, up to 4.5 years