Trial Outcomes & Findings for Randomized Discontinuation Study of Lapatinib Versus Placebo in Subjects With Documented Tumor Progression After Chemotherapy, or Where no Approved Therapy Exists (NCT NCT00447226)

Last Updated: 2012-06-12

Results Overview

Per Response Evaluation Criteria In Solid Tumors (RECIST): Complete response (CR), disappearance of all lesions; partial response (PR), \>=30% decrease in the measurements of the largest lesions; stable disease (SD), insufficient shrinkage to qualify for PR or insufficient increase to qualify for progressive disease (PD); PD, \>=20% increase in measurements of lesions or appearance of new lesions. Data were not fully analyzed due to early study termination.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

Week 12

Results posted on

2012-06-12

Participant Flow

Participants maintaining stable disease (SD) in Stage 1 (open label) were randomized to double-blind lapatinib 1500 milligrams (mg)/day or placebo (Stage 2). Of 32 participants in Stage 1, 7 maintained SD and were randomized into Stage 2. These 7 participants are represented as "completed" in the "Open-label Phase" participant flow table.

Participant milestones

Participant milestones
Measure	Placebo Identical matching placebo orally, once a day	Lapatinib 1500 Milligrams (mg) Lapatinib 1500 mg orally, once a day
12-Week Open-label Phase STARTED	0	32
12-Week Open-label Phase COMPLETED	0	7
12-Week Open-label Phase NOT COMPLETED	0	25
Double-blind Phase STARTED	4	3
Double-blind Phase COMPLETED	0	0
Double-blind Phase NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Identical matching placebo orally, once a day	Lapatinib 1500 Milligrams (mg) Lapatinib 1500 mg orally, once a day
12-Week Open-label Phase Adverse Event	0	3
12-Week Open-label Phase Protocol Violation	0	1
12-Week Open-label Phase Disease Progression	0	20
12-Week Open-label Phase Physician Decision	0	1
Double-blind Phase Disease Progression	4	3

Baseline Characteristics

Randomized Discontinuation Study of Lapatinib Versus Placebo in Subjects With Documented Tumor Progression After Chemotherapy, or Where no Approved Therapy Exists

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=32 Participants All participants treated in the open-label phase (1500 milligrams \[mg\] lapatinib, orally once a day), including those subsequently randomized to lapatinib (1500 mg, orally once a day) or matching placebo
Age Continuous	65 years STANDARD_DEVIATION 10.25 • n=99 Participants
Sex: Female, Male Female	13 Participants n=99 Participants
Sex: Female, Male Male	19 Participants n=99 Participants
Race/Ethnicity, Customized White	31 participants n=99 Participants
Race/Ethnicity, Customized African American/ African heritage	1 participants n=99 Participants

PRIMARY outcome

Timeframe: Week 12

Population: All treated: all participants who received at least one dose of open-label lapatinib.

Outcome measures

Outcome measures
Measure	Open-label Lapatinib 1500 Milligrams (mg) n=32 Participants Open-label lapatinib 1500 mg orally, once a day	Placebo Identical matching placebo orally, once a day	Placebo Identical matching placebo orally, once a day
Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose Complete response	1 participants	—	—
Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose Partial response	0 participants	—	—
Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose Stable disease	9 participants	—	—
Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose Progressive disease	20 participants	—	—
Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose Unknown	2 participants	—	—

PRIMARY outcome

Timeframe: Week 12 after randomization.

Population: Intent-to-Treat Population: all participants randomized to study treatment in Stage 2

The percentage of participants who did not show signs of progressive disease 12 weeks after receiving lapatinib or placebo in Stage 2 of the study (participants who maintained SD in Stage 1 were randomized to either lapatinib or placebo) was measured. Formal statistics for treatment comparison were not performed, due to early study termination. The percentage of participants displayed below includes those with CR + PR + SD.

Outcome measures

Outcome measures
Measure	Open-label Lapatinib 1500 Milligrams (mg) n=3 Participants Open-label lapatinib 1500 mg orally, once a day	Placebo n=4 Participants Identical matching placebo orally, once a day	Placebo Identical matching placebo orally, once a day
Percentage of Participants Who Remained Progression-free 12 Weeks After Randomization	0 percentage of participants	25 percentage of participants	—

SECONDARY outcome

Timeframe: (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib)

Population: All treated: all participants who received at least one dose of open-label lapatinib.

Duration of response was calculated as the time from first documented partial response (PR; \>=30% decrease in the measurements of the largest lesions) or complete response (CR; disappearance of all lesions) until disease progression, the time when the participant began a new anti-cancer therapy, or death. Data were not analyzed due to early study termination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment to disease progression/death (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib)

Population: All treated: all participants who received at least one dose of open-label lapatinib.

Progression-free survival was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored". Data were not analyzed due to early study termination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment to disease progression/death (up to 83.3 weeks)

Population: All Treated: all participants who received at least one dose of open-label lapatinib.

Time to disease progression was calculated as the time from the start of treatment to disease progression or death due to disease progression. For participants who did not progress, the date of last contact was used and for those who died due to other causes, the date of death was used. The word used for such participants was "censored". As the median value in the placebo arm was not reached (2 participants were censored and 2 were ongoing), results for the placebo arm are not displayed in the table below.

Outcome measures

Outcome measures
Measure	Open-label Lapatinib 1500 Milligrams (mg) n=32 Participants Open-label lapatinib 1500 mg orally, once a day	Placebo n=3 Participants Identical matching placebo orally, once a day	Placebo Identical matching placebo orally, once a day
Time to Disease Progression (TTP)	78 weeks Interval 42.0 to 92.0	137 weeks Interval 41.0 to 164.0	—

SECONDARY outcome

Timeframe: Pre-dose and every 6 weeks until withdrawal (up to 84.1 weeks)

Population: Participants with ovarian cancer. The number of participants for whom there are data varies at each time point, depending on how many participants had CA-125 samples.

CA-125 is a "tumor marker", found in greater concentration in tumor cells than other cells of the body. In particular, CA-125 is present in greater concentration in ovarian cancer cells than in other cells. A decreasing level generally indicates that therapy has been effective, whereas an increasing level indicates tumor recurrence.

Outcome measures

Outcome measures
Measure	Open-label Lapatinib 1500 Milligrams (mg) n=10 Participants Open-label lapatinib 1500 mg orally, once a day	Placebo Identical matching placebo orally, once a day	Placebo Identical matching placebo orally, once a day
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 doubled at Week 6, n=3	1 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 halved at Week 6, n=3	0 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 doubled at Week 18, n=2	0 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 halved at Week 18, n=2	0 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 doubled at withdrawal at <=12 weeks, n=4	3 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 halved at withdrawal at <=12 weeks, n=4	0 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 doubled at withdrawal at >12 weeks, n=1	0 participants	—	—
Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 CA-125 halved at withdrawal at >12 weeks, n=1	0 participants	—	—

SECONDARY outcome

Timeframe: Performed on archived tissue collected at screening.

Population: All participants with gastric cancer who were screened to determine their eligibility to enter into the study

The number of gastric cancer participants with MET amplification (determined by fluorescence in situ hybridization \[FISH\] assay) compared to the total number of gastric cancer participants screened was to be recorded. Amplification of the MET gene has been reported to be related to carcinogenesis, progression of gastric cancer, and poor prognosis. Data were not analyzed due to early study termination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening

Population: All participants who were screened to determine their eligibility to enter into the study

The number of ErbB2-positive participants (determined by FISH assay) compared to the total number of participants screened was to be recorded. Over-expression of ErbB2 has been correlated with an overall poor prognosis. Data were not analyzed, due to early study termination.

Outcome measures

Outcome data not reported

Adverse Events

All Participants

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=32 participants at risk All participants treated in the open-label phase (1500 mg lapatinib, orally once a day), including those subsequently randomized to lapatinib (1500 mg, orally once a day) or matching placebo
Nervous system disorders Ataxia	3.1% 1/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Nervous system disorders Cerebral hemorrhage	3.1% 1/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Nervous system disorders Syncope	3.1% 1/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Metabolism and nutrition disorders Hypoglycemia	3.1% 1/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Infections and infestations Cellulitis	3.1% 1/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.

Other adverse events

Other adverse events
Measure	All Participants n=32 participants at risk All participants treated in the open-label phase (1500 mg lapatinib, orally once a day), including those subsequently randomized to lapatinib (1500 mg, orally once a day) or matching placebo
Gastrointestinal disorders Diarrhea	53.1% 17/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
General disorders Fatigue	31.2% 10/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Metabolism and nutrition disorders Anorexia	28.1% 9/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Nausea	28.1% 9/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
General disorders Edema peripheral	21.9% 7/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Vomiting	21.9% 7/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Blood and lymphatic system disorders Anemia	18.8% 6/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Constipation	18.8% 6/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Skin and subcutaneous tissue disorders Dermatitis acneiform	18.8% 6/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Musculoskeletal and connective tissue disorders Back pain	15.6% 5/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Skin and subcutaneous tissue disorders Rash	15.6% 5/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Abdominal pain upper	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Nervous system disorders Dizziness	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Dysphagia	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Psychiatric disorders Insomnia	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
General disorders Pyrexia	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Infections and infestations Upper respiratory tract infection	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Investigations Weight decreased	12.5% 4/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Abdominal pain	9.4% 3/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Metabolism and nutrition disorders Dehydration	9.4% 3/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Skin and subcutaneous tissue disorders Dry skin	9.4% 3/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Metabolism and nutrition disorders Failure to thrive	9.4% 3/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Flatulence	9.4% 3/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Musculoskeletal and connective tissue disorders Pain in extremity	9.4% 3/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Abdominal distension	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Infections and infestations Cellulitis	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Metabolism and nutrition disorders Decreased appetite	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Dyspepsia	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Gastrointestinal disorders Gastroesophageal reflux disease	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Musculoskeletal and connective tissue disorders Groin pain	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Respiratory, thoracic and mediastinal disorders Hemoptysis	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
General disorders Mucosal inflammation	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Musculoskeletal and connective tissue disorders Muscle spasms	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Musculoskeletal and connective tissue disorders Muscular weakness	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Infections and infestations Pneumonia	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Renal and urinary disorders Pollakiuria	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Skin and subcutaneous tissue disorders Pruritus	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Skin and subcutaneous tissue disorders Skin chapped	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Skin and subcutaneous tissue disorders Skin exfoliation	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.
Infections and infestations Urinary tract infection	6.2% 2/32 • All adverse events (AEs) and serious adverse events (SAEs), regardless of relationship to lapatinib, were collected from the first dose until 5 days after the last dose of study medications (up to 84.1 weeks). The AEs and SAEs presented below represent data collected from all participants, whether taking open-label lapatinib or whether randomized to lapatinib/placebo. The SAE of cerebral hemorrhage was reported 2 days after the last dose of study drug was taken and was thus not an "on-treatment" event.

Additional Information

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Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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