Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Myotonic Dystrophy Type 1

All Drugs and Chemicals

Antineoplastic Agents

Pharmaceutical Solutions

Antibodies

Trastuzumab

Trastuzumab deruxtecan

Immunoglobulins

Ado-Trastuzumab Emtansine

Immunoconjugates

Immunologic Factors

T-DM1 resistant/refractory (R/R) patients in the low dose treatment group

T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group

T-DM1 resistant/refractory (R/R) patients in the high dose treatment group

In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm

DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.

DS-8201a

Global Clinical Leader

Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.

HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).

In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.

A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)

A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.

The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.

Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.

Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.

The estimated duration of confirmed response (complete response \[CR\] or partial response \[PR\]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.

The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.

Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.

TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.

AstraZeneca

Daiichi Sankyo Co., Ltd.

Daiichi Sankyo

A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.

T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.

Part 1: DS-8201a Low Dose

T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.

Part 1: DS-8201a Medium Dose

T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.

Part 1: DS-8201a High Dose

All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.

Part 2a: DS-8201a Low Dose

All participants who were T-DM1 intolerant and treated at the recommend dose (5.4 mg/kg) in Part 2b in the continuation phase.

Part 2b (Exploratory): DS-8201a Low Dose

All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 2b in the continuation phase.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

South Korea

Belgium

United States

Japan

Italy

United Kingdom

France

Spain

Region of Enrollment

Contact for Clinical Trial Information

All T-DM1 resistant/refractory (R/R) participants who were treated in Part 1 or Part 2a at the recommended (5.4 mg/kg) dose.

Part 1 and Part 2a: DS-8201a Low Dose

All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.

Part 1 + Part 2a + Part 2b: DS-8201a Low Dose

Objective response rate (ORR) was assessed in the Enrolled Analysis Set.at data cut-off date of 21 March 2019

Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Objective response rate (ORR) was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Complete response

Partial response

Stable disease

Progressive disease

Non-evaluable

All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.

Part 1 + Part 2a: DS-8201a Low Dose

Best overall tumor response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Disease control rate

Clinical benefit rate

Disease control rate (DCR) and clinical benefit rate (CBR) were assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Participants with CR or PR were analyzed. Estimated duration of response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Progression-free survival was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Baseline to Week 6

Baseline to Week 12

Baseline to Week 18

Baseline to Week 24

Baseline to Week 30

Baseline to Week 36

Best percent change from baseline

Best percent change from baseline in sum of diameters was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)

Any TEAE

Drug-related TEAEs

Drug-related TEAEs of CTCAE ≥Grade 3

Any serious TEAE

Drug-related serious TEAEs

TEAEs associated with drug discontinuation

Related TEAEs associated with drug discontinuation

TEAEs associated with dose reduction

Drug-related TEAEs associated with dose reduction

TEAEs associated with dose interruption

Related TEAEs associated with drug interruption

TEAEs associated with death

Drug-related TEAEs associated with death

All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in the continuation phase.

All participants who were T-DM1 intolerant and treated at the recommend dose (5.4 mg/kg) in the continuation phase.

Adverse event data were assessed in the Safety Analysis Set t data cut-off date of 21 March 2019.

Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)

T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phase.

Overall Study

Digestive System Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Amino Acids

Capecitabine

Lapatinib

Antimetabolites

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

oral lapatinib (1250mg) administered as a monotherapy run-in followed by its combination with capecitabine

Lapatinib and Capecitabine

GSK Clinical Trials

The study will determine if changes in expression of markers involved in the 5-FU pathways are associated with response to treatment with the combination of lapatinib and capecitabine independent of tumor erbB2 status.

Study For Patients With Untreated Gastric Cancer Who Will Receive Capecitabine And Lapatinib

An Exploratory, Phase II Trial to Determine the Association of Lapatinib Induced Fluoropyrimidine Gene Changes With Efficacy Parameters of Lapatinib and Capecitabine in First Line Gastric Cancer

Participants were analyzed for intratumoral expression levels of genes involved in the 5-fluorouracil (FU) pathway and lapatinib-targeted genes. Change in biomarker expression levels was calculated as the levels measured after the lapatinib Run-in Period (Baseline) of the study minus the levels measured at the start of monotherapy (Day -7). EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor. Data are presented as ratios of the normalized gene expression of the target gene to that of beta actin.

Response is defined as documented evidence of complete response (CR) or partial response (PR). The investigator evaluated response based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is defined as the disappearance of all target lesions (TLs) and non-TLs and the appearance of no new lesions (NLs). Partial response for TLs is defined as \>= a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD. For non-TLs it is defined as the persistence of 1 or more non-TL and no new TLs or non-TLs.

5-month (mo.) PFS was defined as the percentage of par. who were alive/progression free for 5 months from the time of initial treatment. PFS is defined as the time from the initial treatment until the first observation of disease progression (DP)/death due to any cause; the percentage of par. whose follow-up ended or was ongoing was reported. DP is defined as symptomatic progression or the appearance of \>=1 NL and/or unequivocal progression of existing non-TLs, and a \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since treatment started.

PFS is defined as the time from the initial treatment until the first observation of disease progression or death due to any cause. The date of documented disease progression was defined as the earliest date of radiographic disease assessment progression or symptomatic progression, whichever came first. For participants who did not die/progress, survival was censored at the time of the last assessment (or contact).

Overall survival is defined as the time from the initial treatment until death due to any cause. A death occurring during the study is defined as a death occurring during treatment or within 30 days of the last administration of study medication.

Time to progression is defined as the time from the initial treatment (first dose) until the first documented radiological symptomatic sign of disease progression. Time to progression data are presented as cumulative incidence estimate, which is defined as the time from the initial treatment until crude hazard probability of the occurrence of a particular event is reached to a particular point. All factors that hinder the observation of the event are defined as competing risks.

Time to progression is defined as the time from the initial treatment (first dose) until the first documented radiological symptomatic sign of disease progression. Time to progression data are presented as cumulative incidence estimate, which is defined as the time from the initial treatment until crude hazard probability of occurrence of a particular event is reached to a particular point. All factors that hinder the observation of the event are defined as competing risks.

Time to response is defined as the time from the initial treatment until the first documented evidence of CR (disappearance of all TLs and non-TLs and the appearance of no new lesions) or PR (\>= a 30% decrease in the sum of the longest diameter of TLs, taking as reference the Baseline sum longest diameter) (whichever status was recorded first). Time to response data are presented as cumulative incidence estimate, which is defined as the time from the initial treatment until crude hazard probability of the occurrence of a particular event is reached to a particular point.

Duration of response is defined as the time from the first documented evidence of tumor response (CR or PR) until the first documented sign of disease progression or death due to any cause, whichever came first.

Best overall response was evaluated by the investigator based on RECIST criteria: CR; PR; Stable Disease (SD), defined as no sufficient shrinkage to qualify for PR, no sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD, defined as at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of \>= 1 new lesions; Unknown, defined as participants who do not have CR, PR, SD, or PD.

Toxicity was measured in grades (AE severity) per National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI CTCAE) version (v) 3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For albumin (per blood samples): G 1 (\<lower limit of normal \[LLN\] to 3 grams per deciliter \[g/dL\]), mild; G 2 (\<3 to 2 g/dL), moderate; G 3 (\<2 g/dL), severe; G 4 (value not available), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For ALP: G 1 (upper limit of normal \[ULN\] to 2.5x ULN), mild; G 2 (\>2.5 to 5.0x ULN), moderate; G 3 (\>5.0 to 20.0x ULN), severe; G 4 (\>20.0x ULN), life threatening/disabling; G 5 (value not available), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of AST. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For AST: G 1 (\>ULN to 2.5x ULN), mild; G 2 (\>2.5 to 5.0x ULN), moderate; G 3 (\>5.0 to 20.0x ULN), severe; G 4 (\>20.0x ULN), life threatening/disabling; G 5 (value not available), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of ALT. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For ALT: G 1 (\>ULN to 2.5x ULN), mild; G 2 (\>2.5 to 5.0x ULN), moderate; G 3 (\>5.0 to 20.0x ULN), severe; G 4 (\>20.0x ULN), life threatening/disabling; G 5 (value not available), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of total bilirubin. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For total bilirubin: G 1 (\>ULN to 1.5x ULN), mild; G 2 (\>1.5 to 3.0x ULN), moderate; G 3 (\>3.0 to 10.0x ULN), severe; G 4 (\>10.0x ULN), life threatening/disabling; G 5 (value not available), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for calcium evaluation. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For calcium (low and high, respectively): G 1 (\<LLN to 8.0 mg/dL; \>ULN to 11.5x ULN), mild; G 2 (\<8.0 to 7.0 mg/dL; \>11.5 to 12.5 ULN), moderate; G 3 (\<7.0 to 6.0 mg/dL; \>12.5 to 13.5 mg/dL), severe; G 4 (\<6 mg/dL; \>13.5 mg/dL), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of creatinine. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For creatinine: G 1 (\>ULN to 1.5x ULN), mild; G 2 (\>1.5 to 3.0x ULN), moderate; G 3 (\>3.0 to 6.0x ULN), severe; G 4 (\>6.0x ULN), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of glucose. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For glucose (high and low, respectively): G 1 (\>ULN to 160 mg/dL; \<LLN to 55 mg/dL), mild; G 2 (\>160 to 250 mg/dL; \<55 to 40 mg/dL), moderate; G 3 (\>250 to 500 mg/dL; \<40 to 30 mg/dL), severe; G 4 (\>500 mg/dL; \<30 mg/dL), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For potassium (high and low \[per blood samples\], respectively): G 1 (\>ULN to 5.5 millimoles per liter \[mmol/L\]; \<LLN to 3.0 mmol/L), mild; G 2 (\>5.5 to 6.0 mmol/L; value not available), moderate; G 3 (\>6.0 to 7.0 mmol/L; \<3.0 to 2.5 mmol/L), severe; G 4 (\>7.0 mmol/L; \<2.5 mmol/L), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for magnesium evaluation. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For magnesium (high and low, respectively): G 1 (\>ULN to 3.0 mg/dL; \<LLN to 1.2 mg/dL), mild; G 2 (value not available; \<1.2 to 0.9 mg/dL), moderate; G 3 (\>3.0 to 8.0 mg/dL; \<0.9 to 0.7 mg/dL), severe; G 4 (\>8.0 mg/dL; \<0.7 mg/dL), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for sodium evaluation. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of each AE severity. For sodium (high and low, respectively): G 1 (\>ULN to 150 mmol/L; \<LLN to 130 mmol/L), mild; G 2 (\>150 to 155 mmol/L; value not available), moderate; G 3 (\>155 to 160 mmol/L; \<130 to 120 mmol/L), severe; G 4 (\>160 mmol/L; \<120 mmol/L), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of hemoglobin. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For hemoglobin: G 1 (\<LLN to 10 g/dL), mild; G 2 (\<10.0 to 8.0 g/dL), moderate; G 3 (\<8.0 to 6.5 g/dL), severe; G 4 (\<6.5 g/dL), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of lymphocytes. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For lymphocytes: G 1, mild; G 2, moderate; G 3, severe; G 4, life threatening/disabling; G 5, death related to AE; ranges were provided by local laboratories. Change from Baseline was measured as any grade increase (AGI), increase to G 3 (ItoG3), and increase to G 4 (ItoG4). Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of total neutrophils. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For neutrophils: G 1 (\<LLN to 1500/millimeters cubed \[mm\^3\] of blood plasma \[bp\]), mild; G 2 (\<1500 to 1000/mm\^3 of bp), moderate; G 3 (\<1000 to 500/mm\^3 of bp), severe; G 4 (\<500/mm\^3 of bp), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of platelet count. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For platelet count: G 1 (\<LLN to 75000/mm\^3 of blood plasma \[bp\]), mild; G 2 (\<75000 to 50000/mm\^3 of bp), moderate; G 3 (\<50000 to 25000/mm\^3 of bp), severe; G 4 (\<25000/mm\^3 of bp), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

Blood samples were collected for the evaluation of WBC count. Toxicity was measured in grades (AE severity) per NCI CTCAE, v3.0, displaying Grades (G) 1-5 with unique clinical descriptions of the severity of each AE. For WBCs: G 1 (\<LLN to 3000/mm\^3 of blood plasma \[bp\]), mild; G 2 (\<3000 to 2000/mm\^3 of bp), moderate; G 3 (\<2000 to 1000/mm\^3 of bp), severe; G 4 (\<1000/mm\^3 of bp), life threatening/disabling; G 5 (death), death related to AE. Worst-case on-therapy reflects the most severe change at any time point measured post treatment.

GlaxoSmithKline

Lapatinib tablets were administered orally at a dose of 1250 mg OD and capecitabine tablets were administered orally at a dose of 1000 milligrams per meters squared (mg/m\^2) twice daily (BID) for the first 14 days of each subsequent 21-day cycle. The capecitabine dose schedule was an intermittent regimen consisting of 2 weeks of treatment followed by 1 week of rest (drug-free period). Capecitabine and lapatinib were taken at two different times of the day.

Lapatinib + Capecitabine

Baseline data were collected in members of the Intent-to-Treat Population, comprised of all participants who entered the study and received at least one dose of lapatinib.

White - White/Caucasian/European Heritage

Asian - East Asian Heritage

American Indian or Alaskan Native

Asian - South East Asian Heritage

Race/Ethnicity, Customized

GSK Response Center

Thymidylate synthase (TS), n=34

Deoxypyridinoline (DPD), n=26

EGFR/HER1, n=32

HER2, n=28

HER3, n=33

Lapatinib 250 milligram (mg) tablets administered at a dose of 1250 mg once daily (OD) for 7 days

Intent-to-Treat (ITT) Population: all participants who entered the study and received at least one dose of lapatinib. Only those participants contributing viable samples were analyzed. Different participants contributed samples for different biomarkers.

Change From Start of Run-in Period in Biomarker Expression Levels at Day 0

Response Rate (Measured as the Percentage of Participants With Response [Complete Response or Partial Response])

ITT Population. PFS was censored for participants who did not have an event before data cut off. The last available assessment prior to the data cut off was used for censored participants.

Percentage of Participants (Par.) With 5-month Progression-free Survival (PFS)

ITT Population. OS was censored for participants who did not have an event before data cut off. The last available assessment prior to the data cut off was used for censored participants.

Overall Survival (OS)

ITT Population. Time to progression was censored for participants who did not have an event before data cut off. The last available assessment prior to the data cut off was used for censored participants.

Time to Progression (All Deaths Are Treated as Competing Risk)

Time to Progression (All Deaths Due to Non-PD Are Treated as Competing Risk)

ITT Population. Time to response was censored for participants who did not have an event before data cut off. The last available assessment prior to the data cut off was used for censored participants.

Time to Response

ITT Population. Duration of response was estimated for only the subset of participants who had response. Duration of response was censored for participants who did not have an event before data cut off. The last available assessment prior to the data cut off was used for censored participants.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)	NCT03248492	Breast Cancer	DS-8201a	18 Years -	Daiichi Sankyo
Study For Patients With Untreated Gastric Cancer Who Will Receive Capecitabine And Lapatinib	NCT00526669	Neoplasms, Gast...	Lapatinib and C...	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for metastatic or unresectable