An Open-label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine + Lapatinib in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer (EMILIA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00829166
First received: January 22, 2009
Last updated: January 7, 2014
Last verified: January 2014
Results First Received: February 22, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Trastuzumab emtansine [Kadcyla]
Drug: Lapatinib
Drug: Capecitabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Participant Flow:   Overall Study
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
STARTED     495     496  
COMPLETED     308     262  
NOT COMPLETED     187     234  
Death                 149                 182  
Lost to Follow-up                 3                 1  
Physician's Decision                 4                 2  
Subject's Decision                 28                 48  
Reason Not Specified                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.
Total Total of all reporting groups

Baseline Measures
    Trastuzumab Emtansine     Lapatinib + Capecitabine     Total  
Number of Participants  
[units: participants]
  495     496     991  
Age  
[units: years]
Mean ± Standard Deviation
  52.2  ± 11.0     53.2  ± 10.8     52.7  ± 10.9  
Gender  
[units: participants]
     
Female     494     492     986  
Male     1     4     5  



  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS) Assessed by an Independent Review Committee   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

2.  Primary:   Overall Survival   [ Time Frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months) ]

3.  Primary:   1 and 2 Year Survival   [ Time Frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months) ]

4.  Secondary:   Progression-free Survival (PFS) 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) ]

5.  Secondary:   Objective Response (OR) Assessed by the Independent Review Committee   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

6.  Secondary:   Duration of Objective Response (OR)   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

7.  Secondary:   Clinical Benefit   [ Time Frame: 6 months after randomization ]

8.  Secondary:   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) ]

9.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Prior to treatment, only study-related serious adverse events (SAE) were reported. All AEs and SAEs were reported from the start of treatment until 30 days after treatment. After treatment, only SAEs assessed to be related to treatment were reported.
Additional Description Safety population: Patients who received at least 1 dose of study medication. Safety analyses were based on the actual treatment received.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Other Adverse Events
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Total, other (not including serious) adverse events      
# participants affected / at risk     467/490     473/488  
Blood and lymphatic system disorders      
Thrombocytopenia † 1    
# participants affected / at risk     137/490 (27.96%)     11/488 (2.25%)  
Anaemia † 1    
# participants affected / at risk     51/490 (10.41%)     39/488 (7.99%)  
Neutropenia † 1    
# participants affected / at risk     28/490 (5.71%)     41/488 (8.40%)  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     113/490 (23.06%)     384/488 (78.69%)  
Nausea † 1    
# participants affected / at risk     192/490 (39.18%)     217/488 (44.47%)  
Vomiting † 1    
# participants affected / at risk     90/490 (18.37%)     138/488 (28.28%)  
Constipation † 1    
# participants affected / at risk     124/490 (25.31%)     47/488 (9.63%)  
Dry mouth † 1    
# participants affected / at risk     77/490 (15.71%)     24/488 (4.92%)  
Dyspepsia † 1    
# participants affected / at risk     43/490 (8.78%)     56/488 (11.48%)  
Abdominal pain upper † 1    
# participants affected / at risk     57/490 (11.63%)     41/488 (8.40%)  
Abdominal pain † 1    
# participants affected / at risk     36/490 (7.35%)     45/488 (9.22%)  
Stomatitis † 1    
# participants affected / at risk     16/490 (3.27%)     61/488 (12.50%)  
General disorders      
Fatigue † 1    
# participants affected / at risk     171/490 (34.90%)     136/488 (27.87%)  
Asthenia † 1    
# participants affected / at risk     86/490 (17.55%)     80/488 (16.39%)  
Mucosal inflammation † 1    
# participants affected / at risk     33/490 (6.73%)     93/488 (19.06%)  
Pyrexia † 1    
# participants affected / at risk     79/490 (16.12%)     35/488 (7.17%)  
Oedema peripheral † 1    
# participants affected / at risk     31/490 (6.33%)     37/488 (7.58%)  
Chest pain † 1    
# participants affected / at risk     31/490 (6.33%)     25/488 (5.12%)  
Chills † 1    
# participants affected / at risk     39/490 (7.96%)     14/488 (2.87%)  
Pain † 1    
# participants affected / at risk     32/490 (6.53%)     12/488 (2.46%)  
Hepatobiliary disorders      
Hyperbilirubinaemia † 1    
# participants affected / at risk     6/490 (1.22%)     40/488 (8.20%)  
Infections and infestations      
Upper respiratory tract infection † 1    
# participants affected / at risk     45/490 (9.18%)     35/488 (7.17%)  
Nasopharyngitis † 1    
# participants affected / at risk     41/490 (8.37%)     30/488 (6.15%)  
Urinary tract infection † 1    
# participants affected / at risk     41/490 (8.37%)     17/488 (3.48%)  
Paronychia † 1    
# participants affected / at risk     1/490 (0.20%)     52/488 (10.66%)  
Investigations      
Aspartate aminotransferase increased † 1    
# participants affected / at risk     110/490 (22.45%)     46/488 (9.43%)  
Alanine aminotransferase increased † 1    
# participants affected / at risk     83/490 (16.94%)     43/488 (8.81%)  
Weight decreased † 1    
# participants affected / at risk     32/490 (6.53%)     33/488 (6.76%)  
Blood bilirubin increased † 1    
# participants affected / at risk     14/490 (2.86%)     30/488 (6.15%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     101/490 (20.61%)     113/488 (23.16%)  
Hypokalaemia † 1    
# participants affected / at risk     41/490 (8.37%)     42/488 (8.61%)  
Dehydration † 1    
# participants affected / at risk     9/490 (1.84%)     25/488 (5.12%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     85/490 (17.35%)     38/488 (7.79%)  
Back pain † 1    
# participants affected / at risk     63/490 (12.86%)     50/488 (10.25%)  
Pain in extremity † 1    
# participants affected / at risk     52/490 (10.61%)     51/488 (10.45%)  
Myalgia † 1    
# participants affected / at risk     69/490 (14.08%)     18/488 (3.69%)  
Musculoskeletal pain † 1    
# participants affected / at risk     40/490 (8.16%)     18/488 (3.69%)  
Bone pain † 1    
# participants affected / at risk     33/490 (6.73%)     17/488 (3.48%)  
Muscle spasms † 1    
# participants affected / at risk     32/490 (6.53%)     12/488 (2.46%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     132/490 (26.94%)     68/488 (13.93%)  
Dizziness † 1    
# participants affected / at risk     47/490 (9.59%)     49/488 (10.04%)  
Neuropathy peripheral † 1    
# participants affected / at risk     49/490 (10.00%)     28/488 (5.74%)  
Dysgeusia † 1    
# participants affected / at risk     35/490 (7.14%)     19/488 (3.89%)  
Peripheral sensory neuropathy † 1    
# participants affected / at risk     29/490 (5.92%)     25/488 (5.12%)  
Paraesthesia † 1    
# participants affected / at risk     29/490 (5.92%)     16/488 (3.28%)  
Psychiatric disorders      
Insomnia † 1    
# participants affected / at risk     54/490 (11.02%)     41/488 (8.40%)  
Depression † 1    
# participants affected / at risk     23/490 (4.69%)     25/488 (5.12%)  
Anxiety † 1    
# participants affected / at risk     28/490 (5.71%)     11/488 (2.25%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     83/490 (16.94%)     60/488 (12.30%)  
Epistaxis † 1    
# participants affected / at risk     99/490 (20.20%)     39/488 (7.99%)  
Dyspnoea † 1    
# participants affected / at risk     56/490 (11.43%)     36/488 (7.38%)  
Skin and subcutaneous tissue disorders      
Palmar−Plantar erythrodysaesthesia syndrome † 1    
# participants affected / at risk     6/490 (1.22%)     283/488 (57.99%)  
Rash † 1    
# participants affected / at risk     52/490 (10.61%)     130/488 (26.64%)  
Pruritus † 1    
# participants affected / at risk     26/490 (5.31%)     41/488 (8.40%)  
Dry skin † 1    
# participants affected / at risk     17/490 (3.47%)     49/488 (10.04%)  
Nail disorder † 1    
# participants affected / at risk     11/490 (2.24%)     39/488 (7.99%)  
Dermatitis acneiform † 1    
# participants affected / at risk     2/490 (0.41%)     26/488 (5.33%)  
Skin fissures † 1    
# participants affected / at risk     1/490 (0.20%)     27/488 (5.53%)  
Skin hyperpigmentation † 1    
# participants affected / at risk     2/490 (0.41%)     25/488 (5.12%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.1



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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