Clinical trial NCT00073528: Study Comparing Lapatinib (GW572016) And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Study Comparing GW572016 and Letrozole Versus Letrozole in Subjects With Estrogen/Progesterone Receptor- Positive Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Neoplasms
Keywords: Lapatinib
Letrozole
breast carcinoma
breast cancer
breast lump
HER2 positive metastatic breast cancer
breast cancer positive for human epidermal growth factor receptor 2
HER2
breast cancer progression
estrogen-receptor positive breast cancer
ER
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2003-11-26
Enrollment: 1286
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluated and compared the efficacy and tolerability of lapatinib and letrozole, with letrozole and placebo in post-menopausal women with hormone receptor positive (ER positive and/or PgR positive) advanced or metastatic breast cancer, who had not received prior therapy for advanced or metastatic disease.

Detailed description: Subjects were randomly assigned to receive either lapatinib (1500 mg once daily orally) with letrozole (2.5 mg once daily orally), or letrozole (2.5 mg once daily orally) with placebo (which matched with lapatinib tablet). Randomization was stratified by site of disease (i.e., soft tissue/visceral disease versus bone only disease) and time since prior adjuvant endocrine therapy (\<6 months or ≥ 6 months from discontinuation of adjuvant anti-estrogen therapy (e.g. tamoxifen or raloxifene) or no prior adjuvant antiestrogen therapy). Study therapy was administered daily until disease progression (objective or symptomatic) or withdrawal from therapy (e.g., due to unacceptable toxicity, withdrawal of consent, or other reason). All subjects were to be followed for survival information until death.

On 13 Apr 2015, after the introduction of the Long Term Follow UP (LTFU) phase (per protocol amendment 07), subjects receiving study treatment with lapatinib plus letrozole, or letrozole plus placebo had continued access to this study treatment until the occurrence of one of the following criteria:

* Disease progression (as determined by the Investigator),
* Intercurrent illness that prevented further administration of study treatment
* Drug related AE which was considered by the investigator to warrant permanent discontinuation of study treatment
* The subject decided to withdraw from the study. Investigators collected AEs and/or SAEs related to study participation, until 30 days following study treatment discontinuation. Subjects who were being followed-up for OS but were not taking study medication, were withdrawn from the study.

The study was terminated on 22-Mar-2018 (last subject last visit).

Eligibility criteria: Key inclusion criteria

1. Signed informed consent;
2. Subjects with histologically confirmed invasive breast cancer with stage IV disease at primary diagnosis or at relapse after curative-intent surgery;

   * Subjects with either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
   * If the disease was restricted to a solitary lesion, its neoplastic nature was confirmed by cytology or histology.
3. Tumors that were ER+ and/or PgR+;
4. Post-menopausal female subjects ≥ 18 years of age.
5. ECOG Performance Status of 0 or 1;
6. Subjects who had archived tumor tissue available to compare tumor response with intra-tumoral expression of ErbB1 and ErbB2.
7. Adjuvant therapy with an aromatase inhibitor and / or trastuzumab was allowed; however, treatment was to stop more than 1 year prior (\>12 months) to the first dose of randomized therapy.
8. Subjects must have ended hormonal replacement therapy (HRT) at least 1 month (30 days) prior to receiving the first dose of randomized therapy.

Key exclusion criteria:

1. Pre-menopausal, pregnant, or lactating;
2. Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for advanced or metastatic disease;
3. Bisphosphonate therapy for bone metastases was allowed; however, treatment was to be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, was not permitted;
4. Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy (lapatinib or placebo);
5. Subjects with known history of/clinical evidence of CNS metastases or leptomeningeal carcinomatosis; and / or subjects on concurrent anti-cancer therapies other than letrozole; and / or who have not recovered from toxicities related to prior adjuvant therapy (surgery, radiotherapy, chemotherapy etc.)
6. Subjects with active or uncontrolled infection and/ or with history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.

Primary outcomes:
measure: Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced or Metastatic Breast Cancer as Assessed by the Investigator
timeFrame: From the date of randomization until the date of the first documented progression or date of death from any cause, whichever came first, assessed for up to 46 months
measure: Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
Secondary outcomes:
measure: Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
measure: PFS in Participants in the ITT Population as Assessed by the Investigator
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
measure: Overall Survival in the HER2-Positive Population
timeFrame: From date of randomization until date of death due to any cause, assessed up to 46 months
measure: Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator.
timeFrame: Up to 46 months
measure: Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator.
timeFrame: Up to 46 months
measure: Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population
timeFrame: Up to 46 months
measure: Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Overall Survival in the ITT Population
timeFrame: From date of randomization until date of death due to any cause, assessed up to 46 months
measure: Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants With Evidence of Brain Metastases From the ITT Population
timeFrame: Up to 46 months
measure: TTP for Participants From the ITT Population as Assessed by the Investigator
timeFrame: Up to 46 months
measure: Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits
timeFrame: Day 1 (baseline) visit; Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192 visits; conclusion/withdrawal visit
measure: Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data
timeFrame: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
measure: Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data
timeFrame: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
measure: Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data
timeFrame: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
measure: Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores
timeFrame: Up to 46 months
measure: Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status
timeFrame: Up to 46 months
measure: Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity
timeFrame: Up to 46 months
measure: Number of Participants With Response in Participants With Baseline Serum HER2 Extracellular Domain (ECD) Baseline Values Greater Than 15 Nanograms Per Milliliter (ng/mL) and 15 ng/mL or Lower
timeFrame: Up to 46 months
measure: Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive
timeFrame: Up to 46 months
measure: Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive
timeFrame: Up to 46 months
measure: Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline
timeFrame: Baseline
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Hot Springs
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Jonesboro
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Alhambra
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facility: Novartis Investigative Site
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city: Bakersfield
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state: California
city: Duarte
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facility: Novartis Investigative Site
state: California
city: Fountain Valley
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facility: Novartis Investigative Site
state: California
city: Fresno
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facility: Novartis Investigative Site
state: California
city: Fullerton
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facility: Novartis Investigative Site
state: California
city: La Jolla
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facility: Novartis Investigative Site
state: California
city: Long Beach
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city: Los Angeles
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facility: Novartis Investigative Site
state: California
city: Montebello
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city: Northridge
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facility: Novartis Investigative Site
state: California
city: Oxnard
country: United States
facility: Novartis Investigative Site
state: California
city: Pleasant Hill
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facility: Novartis Investigative Site
state: California
city: Porterville
country: United States
facility: Novartis Investigative Site
state: California
city: Redondo Beach
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Barbara
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facility: Novartis Investigative Site
state: California
city: Santa Maria
country: United States
facility: Novartis Investigative Site
state: California
city: Vallejo
country: United States
facility: Novartis Investigative Site
state: California
city: Vista
country: United States
facility: Novartis Investigative Site
state: California
city: Aurora
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facility: Novartis Investigative Site
state: Colorado
city: Denver
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facility: Novartis Investigative Site
state: Colorado
city: Longmont
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state: Colorado
city: Wheat Ridge
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facility: Novartis Investigative Site
state: Colorado
city: New Haven
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facility: Novartis Investigative Site
state: Connecticut
city: Boca Raton
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state: Florida
city: Boca Raton
country: United States
facility: Novartis Investigative Site
state: Florida
city: Gainesville
country: United States
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state: Florida
city: Gainesville
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facility: Novartis Investigative Site
state: Florida
city: Hollywood
country: United States
facility: Novartis Investigative Site
state: Florida
city: Lakeland
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facility: Novartis Investigative Site
state: Florida
city: Miami
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facility: Novartis Investigative Site
state: Florida
city: Orlando
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facility: Novartis Investigative Site
state: Florida
city: Port Saint Lucie
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state: Florida
city: West Palm Beach
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state: Florida
city: Atlanta
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state: Georgia
city: Marietta
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state: Georgia
city: Savannah
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state: Georgia
city: Peoria
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state: Illinois
city: Skokie
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state: Illinois
city: Indianapolis
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state: Indiana
city: Bettendorf
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state: Iowa
city: Louisville
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state: Kentucky
city: Metairie
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state: Louisiana
city: New Orleans
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facility: Novartis Investigative Site
state: Louisiana
city: Worcester
country: United States
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state: Massachusetts
city: Duluth
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Robbinsdale
country: United States
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state: Minnesota
city: Saint Louis Park
country: United States
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state: Minnesota
city: Saint Charles
country: United States
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state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Omaha
country: United States
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Voorhees
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state: New Jersey
city: Santa Fe
country: United States
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state: New Mexico
city: Manhasset
country: United States
facility: Novartis Investigative Site
state: New York
city: Rochester
country: United States
facility: Novartis Investigative Site
state: New York
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Greenville
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Fargo
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facility: Novartis Investigative Site
state: North Dakota
city: Canton
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state: Ohio
city: Hershey
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
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facility: Novartis Investigative Site
state: Pennsylvania
city: Pittsburgh
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state: Pennsylvania
city: West Columbia
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state: South Carolina
city: Germantown
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facility: Novartis Investigative Site
state: Tennessee
city: Knoxville
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state: Tennessee
city: Amarillo
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
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state: Texas
city: Irving
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city: Ogden
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state: Utah
city: Salt Lake City
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state: Utah
city: Burlington
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state: Vermont
city: Danville
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state: Virginia
city: Richmond
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state: Virginia
city: Seattle
country: United States
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state: Washington
city: Tacoma
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state: Washington
city: Charleston
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state: West Virginia
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Garran
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Douglas
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Redcliffe
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: Bahía
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Mississauga
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Oshawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sudbury
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: Región Metro De Santiago
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Osijek
country: Croatia
facility: Novartis Investigative Site
city: Pula
country: Croatia
facility: Novartis Investigative Site
city: Split
country: Croatia
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Ceske Budejovice
country: Czechia
facility: Novartis Investigative Site
city: Praha 8
country: Czechia
facility: Novartis Investigative Site
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Hillerod
country: Denmark
facility: Novartis Investigative Site
city: Koebenhavn Oe
country: Denmark
facility: Novartis Investigative Site
city: Naestved
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Roskilde
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Angers Cedex 01
country: France
facility: Novartis Investigative Site
city: Besancon
country: France
facility: Novartis Investigative Site
city: Grenoble Cedex 9
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris Cedex 5
country: France
facility: Novartis Investigative Site
city: Pierre Benite Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex9
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Aalen
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Freiburg
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Heidenheim
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Schwetzingen
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Augsburg
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Bayreuth
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Erlangen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Rehling
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Rosenheim
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Goslar
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Leer
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Bonn
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Coesfeld
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Ibbenbueren
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Troisdorf
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Velbert
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Altenkirchen
country: Germany
facility: Novartis Investigative Site
state: Rheinland-Pfalz
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Dresden
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Kiel
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Kiel
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Pinneberg
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Jena
country: Germany
facility: Novartis Investigative Site
state: Thueringen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Kecskemet
country: Hungary
facility: Novartis Investigative Site
city: Kistarcsa
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Tatabanya
country: Hungary
facility: Novartis Investigative Site
city: Cork
country: Ireland
facility: Novartis Investigative Site
city: Dooradoyle
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Galway
country: Ireland
facility: Novartis Investigative Site
city: Tallaght, Dublin
country: Ireland
facility: Novartis Investigative Site
city: Wilton, Cork
country: Ireland
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Parma
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Genova
country: Italy
facility: Novartis Investigative Site
state: Liguria
city: Genova
country: Italy
facility: Novartis Investigative Site
state: Liguria
city: Crema
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Milano
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Gyeonggi-do
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seodaemun-gu, Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Acapulco
country: Mexico
facility: Novartis Investigative Site
state: Guerrero
city: Colima
country: Mexico
facility: Novartis Investigative Site
city: Durango
country: Mexico
facility: Novartis Investigative Site
city: Durango
country: Mexico
facility: Novartis Investigative Site
city: Mexico, D.F.
country: Mexico
facility: Novartis Investigative Site
city: Amersfoort
country: Netherlands
facility: Novartis Investigative Site
city: Delft
country: Netherlands
facility: Novartis Investigative Site
city: Den Haag
country: Netherlands
facility: Novartis Investigative Site
city: Den Haag
country: Netherlands
facility: Novartis Investigative Site
city: Doetinchem
country: Netherlands
facility: Novartis Investigative Site
city: Eindhoven
country: Netherlands
facility: Novartis Investigative Site
city: Heerlen
country: Netherlands
facility: Novartis Investigative Site
city: Leidschendam
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Nieuwegein
country: Netherlands
facility: Novartis Investigative Site
city: Sittard-geleen
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Christchurch
country: New Zealand
facility: Novartis Investigative Site
city: Lahore
country: Pakistan
facility: Novartis Investigative Site
city: Lahore
country: Pakistan
facility: Novartis Investigative Site
city: Rawalpindi
country: Pakistan
facility: Novartis Investigative Site
city: Callao
country: Peru
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Bydogoszcz
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Capital Park
country: South Africa
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
city: Parktown
country: South Africa
facility: Novartis Investigative Site
city: Port Elizabeth
country: South Africa
facility: Novartis Investigative Site
city: Alcala De Henares (Madrid)
country: Spain
facility: Novartis Investigative Site
city: Badalona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Elche
country: Spain
facility: Novartis Investigative Site
city: Girona
country: Spain
facility: Novartis Investigative Site
city: Leganes, Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
city: Mostoles
country: Spain
facility: Novartis Investigative Site
city: Oviedo
country: Spain
facility: Novartis Investigative Site
city: Palma de Mallorca
country: Spain
facility: Novartis Investigative Site
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Vigo ( Pontevedra)
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Sfax
country: Tunisia
facility: Novartis Investigative Site
city: Sousse
country: Tunisia
facility: Novartis Investigative Site
city: Tunis
country: Tunisia
facility: Novartis Investigative Site
city: Tunis
country: Tunisia
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Chelmsford
country: United Kingdom
facility: Novartis Investigative Site
state: Essex
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
state: Lancashire
city: Northwood
country: United Kingdom
facility: Novartis Investigative Site
state: Middlesex
city: Sutton
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
state: West Midlands
city: Huddersfield
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. doi: 10.1200/JCO.2009.23.3734. Epub 2009 Sep 28.
citation: Schwartzberg LS, Franco SX, Florance A, O'Rourke L, Maltzman J, Johnston S. Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor-positive metastatic breast cancer. Oncologist. 2010;15(2):122-9. doi: 10.1634/theoncologist.2009-0240. Epub 2010 Feb 15.
citation: Sherrill B, Amonkar MM, Sherif B, Maltzman J, O'Rourke L, Johnston S. Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib. Oncologist. 2010;15(9):944-53. doi: 10.1634/theoncologist.2010-0012. Epub 2010 Aug 26.
citation: Finn RS, Press MF, Dering J, O'Rourke L, Florance A, Ellis C, Martin AM, Johnston S. Quantitative ER and PgR assessment as predictors of benefit from lapatinib in postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Clin Cancer Res. 2014 Feb 1;20(3):736-43. doi: 10.1158/1078-0432.CCR-13-1260. Epub 2013 Nov 6.
citation: Prat A, Cheang MC, Galvan P, Nuciforo P, Pare L, Adamo B, Munoz M, Viladot M, Press MF, Gagnon R, Ellis C, Johnston S. Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib. JAMA Oncol. 2016 Oct 1;2(10):1287-1294. doi: 10.1001/jamaoncol.2016.0922.
citation: Wedam SB, Beaver JA, Amiri-Kordestani L, Bloomquist E, Tang S, Goldberg KB, Sridhara R, Ibrahim A, Kim G, Kluetz P, McKee A, Pazdur R. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments. J Clin Oncol. 2018 Apr 20;36(12):1225-1231. doi: 10.1200/JCO.2017.74.6917. Epub 2018 Mar 9.