A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer (EMILIA)

• ClinicalTrials.gov Identifier: NCT00829166
• Recruitment Status: Completed
• First Posted: January 26, 2009
• Results First Posted: April 23, 2013
• Last Update Posted: October 31, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This is a Phase III, randomized, multicenter, international, 2-arm, open-label clinical trial designed to compare the safety and efficacy of trastuzumab emtansine (T-DM1) with that of capecitabine + lapatinib in participants with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination. Once disease progression is reported, all participants will be followed for survival every 3 months until death, loss to follow-up, withdrawal of consent, or study termination.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Trastuzumab emtansine; Drug: Lapatinib; Drug: Capecitabine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 991 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Phase III Open-label Study of the Efficacy and Safety of Trastuzumab MCC-DM1 vs. Capecitabine + Lapatinib in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy
• Study Start Date: February 2009
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Trastuzumab emtansine; Participants will receive trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until disease progression (PD) (as assessed by the investigator), unmanageable toxicity, or study termination.	Drug: Trastuzumab emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle.; Other Names: T-DM1; Trastuzumab-MCC-DM1; RO5304020
Active Comparator: Lapatinib + Capecitabine; Participants will receive lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 milligrams per square meter (mg/m^2) orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Eligible participants will cross over to receive trastuzumab emtansine if second interim analysis demonstrates statistically significant overall survival benefit in favor of trastuzumab emtansine.	Drug: Lapatinib; Lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle.; Other Names: Tykerb; Tyverb; Drug: Capecitabine; Capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.; Other Name: Xeloda

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With PD or Death as Assessed by an Independent Review Committee (IRC) [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   PD was assessed by an IRC using modified Response Evaluation Criteria in Solid Tumors (RECIST). All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as target lesions (TLs) and recorded at baseline. TLs should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements either by imaging or clinically. A sum of the longest diameter for all TLs was calculated as baseline sum longest diameter (SLD). All other lesions (or sites of disease) should be identified as non-TLs and recorded at baseline. PD for TLs was defined as greater than or equal to (>/=) 20 percent (%) increase in SLD, taking as reference smallest SLD recorded since treatment started or appearance of 1 or more new lesions. PD for non-TLs was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Percentage of Participants with PD by IRC or death from any cause was reported.
2. Progression-free Survival (PFS) as Assessed by an IRC (Co-primary Endpoint) [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Tumor response was assessed by an IRC according to modified RECIST. All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs (on the basis of their size and their suitability for accurate repeated measurements either by imaging or clinically) and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. All other lesions were identified as non-TLs and recorded at baseline. PD for TLs: >/= 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or appearance of 1 or more new lesions. PD for non-TLs: appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. PFS: time from randomization to first documented PD by IRC or death from any cause (whichever occurred earlier). The median duration of PFS was estimated using Kaplan-Meier method. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.
3. Percentage of Participants Who Died: Second Interim Analysis [ Time Frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months) ]
   The percentage of participants who died from any cause was reported. The results are reported from second interim analysis, which deemed to be the confirmatory.
4. Overall Survival: Second Interim Analysis (Co-primary Endpoint) [ Time Frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months) ]
   OS was defined as the time from the date of randomization to the date of death from any cause. The median duration of OS was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley. The results are reported from second interim analysis, which deemed to be the confirmatory.
5. Percentage of Participants Who Died: Final Analysis [ Time Frame: From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months) ]
   The percentage of participants who died from any cause was reported. The results reported are from the final analysis. The final analysis is descriptive.
6. Overall Survival: Final Analysis [ Time Frame: From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months) ]
   OS was defined as the time from the date of randomization to the date of death from any cause. The median duration of OS was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley. The results reported are from the final analysis. The final analysis is descriptive.
7. Percentage of Participants Who Were Alive at Year 1 [ Time Frame: Year 1 ]
   1 year survival was defined as the percentage of participants alive 1 year after starting treatment. The results reported are from the final analysis.
8. Percentage of Participants Who Were Alive at Year 2 [ Time Frame: Year 2 ]
   2 year survival was defined as the percentage of participants alive 2 years after starting treatment. The results reported are from the final analysis.

Secondary Outcome Measures :

1. Percentage of Participants With PD or Death as Assessed by the Investigator [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   PD was assessed by the investigator using modified RECIST. All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. PD for TLs was defined as >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. The percentage of participants who died or experienced PD by Investigator was reported.
2. PFS as Assessed by the Investigator [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Tumor response was assessed by the investigator according to modified RECIST. All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. PD for TLs was defined as >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. PFS was defined as the time from randomization to first documented PD by Investigator or death from any cause (whichever occurred earlier). The median duration of PFS was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley.
3. Percentage of Participants With Objective Response (OR) as Assessed by an IRC [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Tumor response was assessed by an IRC according to modified RECIST. OR was defined as the percentage of participants with a complete response (CR) or partial response (PR). All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as >/= 30% decrease in the SLD of TLs, taking as reference the baseline SLD. For non-TLs, a CR was defined as the disappearance of all non-TLs and a PR was defined as the persistence of 1 or more non-TLs. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. Participants without a post-baseline tumor assessment were considered non-responders. The percentage of participants with CR or PR by IRC was reported. The 95% CI was computed using Blyth-Still Casella exact CI method.
4. Duration of Objective Response (DOR) as Assessed by an IRC [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Tumor response was assessed by an IRC according to modified RECIST. DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier. OR was defined as a CR or PR determined on 2 consecutive tumor assessments at least 4 weeks apart. For TLs, CR was defined as the disappearance of all TLs; PR was defined as >/=30% decrease in the SLD of TLs, taking as reference the baseline SLD; and PD was defined as >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, CR was defined as the disappearance of all non-TLs; PR was defined as the persistence of 1 or more non-TLs; and PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. The 95% CI was computed using the method of Brookmeyer and Crowley.
5. Percentage of Participants With Clinical Benefit as Assessed by an IRC [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Tumor response was assessed by an IRC according to modified RECIST. Participants were considered as experienced clinical benefit if they had an OR or maintained stable disease (SD) for at least 6 months from randomization. OR: CR or PR determined on 2 consecutive tumor assessments >/=4 weeks apart. For TLs, CR: disappearance of all TLs; PR: >/=30% decrease in the SLD of TLs, taking as reference the baseline SLD; PD: >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or appearance of 1 or more new lesions; and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For non-TLs, CR: disappearance of all non-TLs; PR/SD: persistence of 1 or more non-TLs; and PD: appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Participants without a post-baseline tumor assessment were considered non-responders. The 95% CI was computed using Blyth-Still Casella exact CI method.
6. Percentage of Participants With Treatment Failure [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Treatment failure was defined as discontinuation of treatment for any reason, including PD (per investigator review), treatment toxicity, or death from any cause. For "Lapatinib + Capecitabine" arm, a participant was considered as treatment failure only if both drugs were discontinued. For TLs, PD was defined as >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Percentage of participants with treatment failure was reported.
7. Time to Treatment Failure [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Time to treatment failure was defined as the time from randomization to discontinuation of treatment for any reason, including PD (per investigator review), treatment toxicity, or death from any cause. For "Lapatinib + Capecitabine" arm, a participant was considered as treatment failure only if both drugs were discontinued with treatment failure date as the later of the 2 discontinuation dates. For TLs, PD was defined as >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. The median time to treatment failure was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley.
8. Percentage of Participants With Symptom Progression [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Symptom progression was defined as the documentation of a >/= 5-point decrease from baseline in the scoring of responses as measured by the Functional Assessment of Cancer Therapy-for participants with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contained 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer participants (breast cancer subscale [BCS]). All items in the questionnaire were rated by the participant on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96 with higher score indicating better perceived quality of life. The percentage of participants with symptom progression was reported.
9. Time to Symptom Progression [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]
   Time to symptom progression was defined as the time from randomization to the first documentation of a >/= 5-point decrease from baseline in the scoring of responses as measured by the FACT-B questionnaire with the TOI-PFB subscale. The FACT-B TOI-PFB subscale contained 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer participants (BCS). All items in the questionnaire were rated by the participant on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96 with higher score indicating better perceived quality of life. The median time to symptom progression was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results
• Histologically or cytologically confirmed invasive breast cancer
• Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent
• Documented progression (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator
• Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded
• Cardiac ejection fraction greater than or equal to (>/=) 50 percent (%) by either echocardiogram or multi-gated acquisition scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception; contraception use should continue for the duration of the study treatment and for at least 6 months after the last dose of study treatment

Exclusion Criteria:

• History of treatment with trastuzumab emtansine
• Prior treatment with lapatinib or capecitabine
• Peripheral neuropathy of Grade >/= 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers with a similar curative outcome as those mentioned above
• History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization except hormone therapy, which could be given up to 7 days prior to randomization; recovery of treatment-related toxicity consistent with other eligibility criteria
• History of radiation therapy within 14 days of randomization
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization
• History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction or unstable angina within 6 months of randomization
• Current dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy
• Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease)
• Pregnancy or lactation
• Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
• Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis
• History of intolerance (such as Grade 3-4 infusion reaction) to trastuzumab
• Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency
• Current treatment with sorivudine or its chemically related analogs, such as brivudine

Contacts and Locations

Locations

United States, Arizona

Chandler, Arizona, United States, 85224

Tucson, Arizona, United States, 85719

United States, California

Anaheim, California, United States, 92801

Anaheim, California, United States, 92807

Bakersfield, California, United States, 93309

Baldwin Park, California, United States, 91706

Bellflower, California, United States, 90706

Duarte, California, United States, 91010

Fontana, California, United States, 92335

Hayward, California, United States, 94545

Irvine, California, United States, 92618

La Jolla, California, United States, 92093

La Mesa, California, United States, 91942

Loma Linda, California, United States, 92354

Long Beach, California, United States, 90806

Los Angeles, California, United States, 90025

Los Angeles, California, United States, 90034

Los Angeles, California, United States, 90057

Los Angeles, California, United States, 90095-1772

Montebello, California, United States, 90640

Newport Beach, California, United States, 92660

Oakland, California, United States, 94611

Panorama City, California, United States, 91402

Riverside, California, United States, 92505

Roseville, California, United States, 95661

Sacramento, California, United States, 95825

San Diego, California, United States, 92120

San Diego, California, United States, 92123

San Francisco, California, United States, 94115

San Jose, California, United States, 95119

Santa Clara, California, United States, 95051

Santa Maria, California, United States, 93454

Santa Monica, California, United States, 90404

South San Francisco, California, United States, 94080

Thousand Oaks, California, United States, 91360

Vallejo, California, United States, 94589

Walnut Creek, California, United States, 94596

Woodland Hills, California, United States, 91367

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Fort Collins, Colorado, United States, 80528

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Norwalk, Connecticut, United States, 06856

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Stamford, Connecticut, United States, 06902

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Washington, District of Columbia, United States, 20010

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Jacksonville, Florida, United States, 32205

Jacksonville, Florida, United States, 32207

Jacksonville, Florida, United States, 32256

Jacksonville, Florida, United States, 32258

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Lakeland, Florida, United States, 33804-1057

Miami, Florida, United States, 33133

Miami, Florida, United States, 33136

Miami, Florida, United States, 33176

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Atlanta, Georgia, United States, 30322

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Atlanta, Georgia, United States, 30342

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Chicago, Illinois, United States, 60612

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Bettendorf, Iowa, United States, 52722

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Wichita, Kansas, United States, 67214-3728

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Paducah, Kentucky, United States, 42001

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Covington, Louisiana, United States, 70433

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New Orleans, Louisiana, United States, 70115

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Kittery, Maine, United States, 03904

Wells, Maine, United States, 04090

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Baltimore, Maryland, United States, 21202

Baltimore, Maryland, United States, 21237

Bethesda, Maryland, United States, 20817

Rockville, Maryland, United States, 20850

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Boston, Massachusetts, United States, 02114

Boston, Massachusetts, United States, 02115

Boston, Massachusetts, United States, 02118

Boston, Massachusetts, United States, 02215

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Brownstown, Michigan, United States, 48183

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Detroit, Michigan, United States, 48201

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West Bloomfield, Michigan, United States, 48322

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Edina, Minnesota, United States, 55414

Maplewood, Minnesota, United States, 55109

Minneapolis, Minnesota, United States, 55454

Saint Louis Park, Minnesota, United States, 55426

Saint Paul, Minnesota, United States, 55101

St. Louis Park, Minnesota, United States, 55426

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Joplin, Missouri, United States, 64804

Kansas City, Missouri, United States, 64111

Saint Louis, Missouri, United States, 63110

Saint Peters, Missouri, United States, 63110

St. Louis, Missouri, United States, 63141

St. Peters, Missouri, United States, 63376

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Missoula, Montana, United States, 59802

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Omaha, Nebraska, United States, 68114

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Henderson, Nevada, United States, 89052

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Cherry Hill, New Jersey, United States, 08002

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Santa Fe, New Mexico, United States, 87505

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Brockport, New York, United States, 14420

Canandaigua, New York, United States, 14424

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Geneva, New York, United States, 14456

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Lake Success, New York, United States, 11042

Mount Kisco, New York, United States, 10549

Rochester, New York, United States, 14626

Stony Brook, New York, United States, 11794

United States, North Carolina

Charlotte, North Carolina, United States, 28203

Durham, North Carolina, United States, 27710

Hickory, North Carolina, United States, 28602

Kinston, North Carolina, United States, 28501

Washington, North Carolina, United States, 27889

United States, Ohio

Cleveland, Ohio, United States, 44106

Cleveland, Ohio, United States, 44195

Columbus, Ohio, United States, 43215

Columbus, Ohio, United States, 43219

Columbus, Ohio, United States, 43228

Middletown, Ohio, United States, 45042

Newark, Ohio, United States, 43055

Sandusky, Ohio, United States, 44870

United States, Oregon

Portland, Oregon, United States, 97227

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19106

Philadelphia, Pennsylvania, United States, 19124

Pittsburgh, Pennsylvania, United States, 15213

Pittsburgh, Pennsylvania, United States, 15232

United States, Rhode Island

East Providence, Rhode Island, United States, 02915

United States, South Carolina

Columbia, South Carolina, United States, 29210

North Charleston, South Carolina, United States, 29425

United States, Tennessee

Memphis, Tennessee, United States, 38120

Nashville, Tennessee, United States, 37203

United States, Texas

Austin, Texas, United States, 78731

Bryan, Texas, United States, 77802

Cypress, Texas, United States, 77429

Dallas, Texas, United States, 75230

El Paso, Texas, United States, 79902

Houston, Texas, United States, 77090

Shenandoah, Texas, United States, 77384

Temple, Texas, United States, 76501

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Fairfax, Virginia, United States, 22031

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Gig Harbor, Washington, United States, 98332

Lakewood, Washington, United States, 98499

Puyallup, Washington, United States, 98372

Tacoma, Washington, United States, 98405

United States, Wisconsin

Milwaukee, Wisconsin, United States, 53226

Wausau, Wisconsin, United States, 54401

Bosnia and Herzegovina

Banja Luka, Bosnia and Herzegovina, 78000

Sarajewo, Bosnia and Herzegovina, 71000

Brazil

Belo Horizonte, Brazil, 30150-281

Curitiba, Brazil, 80530-010

Goiania, Brazil, 74605-070

Itajai, Brazil, 88301-220

JAU, Brazil, 17210-080

Joao Pessoa, Brazil, 58040280

Porto Alegre - Rs, Brazil, 90050-170

Porto Alegre, Brazil, 90430-090

Porto Alegre, Brazil, 90610-000

Porto Alegre, Brazil, 91350-200

Rio de Janeiro, Brazil, 20560-120

Rio de Janeiro, Brazil, 22260-020

Santo Andre, Brazil, 09060-870

Sao Paulo, Brazil, 01317-000

Sao Paulo, Brazil, 1323020

Bulgaria

Plovdiv, Bulgaria, 4000

Sofia, Bulgaria, 1756

Sofia, Bulgaria, 1784

Varna, Bulgaria, 9002

Canada, Alberta

Calgary, Alberta, Canada, T2N 4N2

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

Kelowna, British Columbia, Canada, V1Y 5L3

Vancouver, British Columbia, Canada, V5Z 1H5

Canada, Nova Scotia

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

Ottawa, Ontario, Canada, K1H 8L6

Sudbury, Ontario, Canada, J9P 3Y1

Toronto, Ontario, Canada, M4N 3M5

Canada, Quebec

Greenfield Park, Quebec, Canada, J4V 2H1

Montreal, Quebec, Canada, H1T 2M4

Montreal, Quebec, Canada, H2W 1T8

Montreal, Quebec, Canada, H3T 1E2

Colombia

Bogota, Colombia, 0

Bogota, Colombia, 49 00

Monteria, Colombia

Denmark

Herlev, Denmark, 2730

København, Denmark, 2100

Odense, Denmark, 5000

Finland

Helsinki, Finland, 00180

Tampere, Finland, 33520

Turku, Finland, 20520

France

Avignon, France, 84082

Bordeaux, France, 33076

Brest, France, 29609

Caen, France, 14076

Dijon, France, 21079

La Roche Sur Yon, France, 85925

Montpellier, France, 34298

Paris, France, 75248

Saint Brieuc, France, 22015

Saint Herblain, France, 44805

Vandoeuvre-les-nancy, France, 54511

Germany

Aschaffenburg, Germany, 63739

Berlin, Germany, 10367

Berlin, Germany, 13125

Berlin, Germany, 4169

Bonn, Germany, 53113

Dortmund, Germany, 44137

Freiburg, Germany, 79106

Fuerstenwalde, Germany, 15517

Hamburg, Germany, 20357

Karlsruhe, Germany, 76135

Kiel, Germany, 24105

Offenbach, Germany, 63069

Stralsund, Germany, 18435

Hong Kong

Hong Kong, Hong Kong

India

Bangalore, India, 560027

Gurgaon, India, 122001

Kolkata, India, 700 053

New Delhi, India, 110029

Pune, India, 411004

Italy

Aviano, Italy, 33081

Bologna, Italy, 40138

Candiolo, Italy, 10060

Genova, Italy, 16132

Meldola, Italy, 47014

Milano, Italy, 20133

Milano, Italy, 20141

Napoli, Italy, 80131

Negrar, Italy, 37024

Pisa, Italy, 56100

Reggio Emilia, Italy, 42100

Roma, Italy, 00168

Rozzano, Italy, 20089

Sassari, Italy, 07100

Terni, Italy, 05100

Korea, Republic of

Kyunggi-do, Korea, Republic of, 411-769

Seoul, Korea, Republic of, 110-744

Seoul, Korea, Republic of, 120-752

Seoul, Korea, Republic of, 135-710

Mexico

Acapulco, Mexico, 39670

Oaxaca, Mexico, 68000

Toluca, Mexico, 50180

New Zealand

Newtown, New Zealand, 6021

Palmerston North, New Zealand, 4442

Philippines

Diliman, Quezon City, Philippines, 1100

Quezon City, Luzon, Philippines, 1101

Poland

Bialystok, Poland, 15-027

Gdansk, Poland, 80-952

Krakow, Poland, 31-531

Lublin, Poland, 20-090

Opole, Poland, 45-060

Poznan, Poland, 61-866

Warszawa, Poland, 02-781

Portugal

Coimbra, Portugal, 3000-075

Lisboa, Portugal, 1649-035

Porto, Portugal, 4200-072

Russian Federation

Kemerovo, Russian Federation, 650036

Moscow, Russian Federation, 121356

St Petersburg, Russian Federation, 197758

Singapore

Singapore, Singapore, 119074

Singapore, Singapore, 169610

Slovenia

Ljubljana, Slovenia, 1000

Spain

Barcelona, Spain, 08035

Córdoba, Spain, 14004

Lerida, Spain, 25198

Madrid, Spain, 28041

Madrid, Spain, 28046

Santander, Spain, 39008

Sevilla, Spain, 41013

Valencia, Spain, 46009

Zaragoza, Spain, 50009

Sweden

Eskilstuna, Sweden, 63188

Gaelve, Sweden, 80187

Goteborg, Sweden, 40036

Switzerland

Luzern, Switzerland, 6004

St. Gallen, Switzerland, 9007

Taiwan

Kaohsung, Taiwan, 883

Taichung, Taiwan, 404

Taichung, Taiwan, 407

Taipei, Taiwan, 112

Taoyuan, Taiwan, 333

United Kingdom

Bournemouth, United Kingdom, BH7 7DW

Cardiff, United Kingdom, CF14 2TL

Denbigh, United Kingdom, LL18 5UJ

London, United Kingdom, SE1 7EH

London, United Kingdom, SW3 6JJ

Manchester, United Kingdom, M20 4BX

New Castle Upon Tyne, United Kingdom, NE7 7DN

Northwood, United Kingdom, HA6 2RN

Poole, United Kingdom, BH15 2JB

Preston, United Kingdom, PR2 9HT

Romford, United Kingdom, RM7 0AG

Sutton, United Kingdom, SM2 5PT

Weston Super Mare, United Kingdom, BS23 4TQ

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dieras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. doi: 10.1016/S1470-2045(17)30312-1. Epub 2017 May 16. Erratum In: Lancet Oncol. 2017 Aug;18(8):e433. Lancet Oncol. 2018 Dec;19(12):e667.

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. doi: 10.1056/NEJMoa1209124. Epub 2012 Oct 1. Erratum In: N Engl J Med. 2013 Jun 20;368(25):2442.

Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00829166
• Other Study ID Numbers: BO21977; TDM4370g ( Other Identifier: Genentech )
• First Posted: January 26, 2009
• Results First Posted: April 23, 2013
• Last Update Posted: October 31, 2016
• Last Verified: September 2016

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Capecitabine; Trastuzumab; Lapatinib; Maytansine; Ado-Trastuzumab Emtansine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Immunotoxins; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs