Clinical trial NCT00829166: A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-01-26
Enrollment: 991
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With PD or Death as Assessed by an Independent Review Committee (IRC)
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Progression-free Survival (PFS) as Assessed by an IRC (Co-primary Endpoint)
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Percentage of Participants Who Died: Second Interim Analysis
timeFrame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
measure: Overall Survival: Second Interim Analysis (Co-primary Endpoint)
timeFrame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
measure: Percentage of Participants Who Died: Final Analysis
timeFrame: From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months)
measure: Overall Survival: Final Analysis
timeFrame: From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months)
measure: Percentage of Participants Who Were Alive at Year 1
timeFrame: Year 1
measure: Percentage of Participants Who Were Alive at Year 2
timeFrame: Year 2
Secondary outcomes:
measure: Percentage of Participants With PD or Death as Assessed by the Investigator
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: PFS as Assessed by the Investigator
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Percentage of Participants With Objective Response (OR) as Assessed by an IRC
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Duration of Objective Response (DOR) as Assessed by an IRC
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Percentage of Participants With Clinical Benefit as Assessed by an IRC
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Percentage of Participants With Treatment Failure
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Time to Treatment Failure
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Percentage of Participants With Symptom Progression
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
measure: Time to Symptom Progression
timeFrame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Anaheim
country: United States
state: California
city: Bakersfield
country: United States
state: California
city: Baldwin Park
country: United States
state: California
city: Bellflower
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state: California
city: Duarte
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state: California
city: Fontana
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state: California
city: Hayward
country: United States
state: California
city: Irvine
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state: California
city: La Jolla
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state: California
city: La Mesa
country: United States
state: California
city: Loma Linda
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Montebello
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Oakland
country: United States
state: California
city: Panorama City
country: United States
state: California
city: Riverside
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Jose
country: United States
state: California
city: Santa Clara
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: South San Francisco
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Woodland Hills
country: United States
state: California
city: Fort Collins
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state: Colorado
city: Norwalk
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state: Connecticut
city: Norwich
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state: Connecticut
city: Stamford
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state: Connecticut
city: Washington
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state: District of Columbia
city: Boca Raton
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state: Florida
city: Fernandina Beach
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state: Florida
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state: Florida
city: Ft. Lauderdale
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state: Florida
city: Hollywood
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state: Florida
city: Jacksonville
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state: Florida
city: Jacksonville
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state: Florida
city: Jacksonville
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city: Jacksonville
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city: Atlanta
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state: Georgia
city: Atlanta
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city: Atlanta
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state: Georgia
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state: Georgia
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state: Georgia
city: Decatur
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state: Georgia
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state: Georgia
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state: Georgia
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city: Meridian
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state: Idaho
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city: Decatur
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city: Effingham
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city: Joliet
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city: Morris
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state: Iowa
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state: Kansas
city: Paducah
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city: Covington
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city: Lafayette
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city: Marrero
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city: Metairie
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city: New Orleans
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state: Maine
city: Wells
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state: Maine
city: York
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state: Maine
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city: Baltimore
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state: Maryland
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state: Maryland
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country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Boston
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city: Boston
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state: Massachusetts
city: Burlington
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city: Peabody
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state: Michigan
city: Dearborn
country: United States
state: Michigan
city: Detroit
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city: Detroit
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state: Michigan
city: Saint Joseph
country: United States
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city: West Bloomfield
country: United States
state: Michigan
city: Edina
country: United States
state: Minnesota
city: Maplewood
country: United States
state: Minnesota
city: Minneapolis
country: United States
state: Minnesota
city: Saint Louis Park
country: United States
state: Minnesota
city: Saint Paul
country: United States
state: Minnesota
city: St. Louis Park
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state: Minnesota
city: Joplin
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state: Missouri
city: Kansas City
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state: Missouri
city: Saint Louis
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state: Missouri
city: Saint Peters
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state: Missouri
city: St. Louis
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city: Omaha
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state: Nebraska
city: Henderson
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state: Nevada
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state: New Jersey
city: Hackensack
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state: New Jersey
city: Morristown
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city: Voorhees
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state: Texas
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state: Washington
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state: Washington
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state: Wisconsin
city: Banja Luka
country: Bosnia and Herzegovina
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city: Curitiba
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city: JAU
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city: Joao Pessoa
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city: Porto Alegre - Rs
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city: Porto Alegre
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city: Porto Alegre
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city: Porto Alegre
country: Brazil
city: Rio de Janeiro
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city: Rio de Janeiro
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city: Santo Andre
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city: Sao Paulo
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city: Sao Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Edmonton
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state: Alberta
city: Kelowna
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state: British Columbia
city: Vancouver
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state: British Columbia
city: Halifax
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state: Nova Scotia
city: Ottawa
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state: Ontario
city: Sudbury
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state: Ontario
city: Toronto
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state: Ontario
city: Greenfield Park
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state: Quebec
city: Montreal
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state: Quebec
city: Montreal
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state: Quebec
city: Montreal
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state: Quebec
city: Bogota
country: Colombia
city: Bogota
country: Colombia
city: Monteria
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city: Herlev
country: Denmark
city: København
country: Denmark
city: Odense
country: Denmark
city: Helsinki
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Avignon
country: France
city: Bordeaux
country: France
city: Brest
country: France
city: Caen
country: France
city: Dijon
country: France
city: La Roche Sur Yon
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Saint Brieuc
country: France
city: Saint Herblain
country: France
city: Vandoeuvre-les-nancy
country: France
city: Aschaffenburg
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Dortmund
country: Germany
city: Freiburg
country: Germany
city: Fuerstenwalde
country: Germany
city: Hamburg
country: Germany
city: Karlsruhe
country: Germany
city: Kiel
country: Germany
city: Offenbach
country: Germany
city: Stralsund
country: Germany
city: Hong Kong
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city: Bangalore
country: India
city: Gurgaon
country: India
city: Kolkata
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Aviano
country: Italy
city: Bologna
country: Italy
city: Candiolo
country: Italy
city: Genova
country: Italy
city: Meldola
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Negrar
country: Italy
city: Pisa
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Rozzano
country: Italy
city: Sassari
country: Italy
city: Terni
country: Italy
city: Kyunggi-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Acapulco
country: Mexico
city: Oaxaca
country: Mexico
city: Toluca
country: Mexico
city: Newtown
country: New Zealand
city: Palmerston North
country: New Zealand
city: Diliman, Quezon City
country: Philippines
city: Quezon City, Luzon
country: Philippines
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Opole
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Ljubljana
country: Slovenia
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: Lerida
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Eskilstuna
country: Sweden
city: Gaelve
country: Sweden
city: Goteborg
country: Sweden
city: Luzern
country: Switzerland
city: St. Gallen
country: Switzerland
city: Kaohsung
country: Taiwan
city: Taichung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Bournemouth
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Denbigh
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: New Castle Upon Tyne
country: United Kingdom
city: Northwood
country: United Kingdom
city: Poole
country: United Kingdom
city: Preston
country: United Kingdom
city: Romford
country: United Kingdom
city: Sutton
country: United Kingdom
city: Weston Super Mare
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.