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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

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
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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.

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.

Serious Adverse Events
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Total, serious adverse events      
# participants affected / at risk     76/490 (15.51%)     88/488 (18.03%)  
Blood and lymphatic system disorders      
Thrombocytopenia † 1    
# participants affected / at risk     3/490 (0.61%)     1/488 (0.20%)  
Febrile neutropenia † 1    
# participants affected / at risk     0/490 (0.00%)     2/488 (0.41%)  
Neutropenia † 1    
# participants affected / at risk     1/490 (0.20%)     1/488 (0.20%)  
Anaemia of malignant disease † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Cardiac disorders      
Pericardial effusion † 1    
# participants affected / at risk     0/490 (0.00%)     2/488 (0.41%)  
Angina pectoris † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Atrial fibrillation † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Cardiomyopathy † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Coronary artery disease † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Pericarditis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Supraventricular tachycardia † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Ear and labyrinth disorders      
Vertigo † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     2/490 (0.41%)     17/488 (3.48%)  
Vomiting † 1    
# participants affected / at risk     6/490 (1.22%)     9/488 (1.84%)  
Abdominal pain † 1    
# participants affected / at risk     4/490 (0.82%)     2/488 (0.41%)  
Nausea † 1    
# participants affected / at risk     1/490 (0.20%)     3/488 (0.61%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     2/490 (0.41%)     0/488 (0.00%)  
Ileus † 1    
# participants affected / at risk     0/490 (0.00%)     2/488 (0.41%)  
Colitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Constipation † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Enteritis † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Gastric ulcer † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Gastritis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Gastrointestinal obstruction † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Ileal fistula † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Intestinal obstruction † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Peptic ulcer haemorrhage † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
General disorders      
Pyrexia † 1    
# participants affected / at risk     7/490 (1.43%)     3/488 (0.61%)  
Pain † 1    
# participants affected / at risk     2/490 (0.41%)     1/488 (0.20%)  
Chest pain † 1    
# participants affected / at risk     2/490 (0.41%)     0/488 (0.00%)  
Asthenia † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Fatigue † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Injection site extravasation † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Mucosal inflammation † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Multi-organ failure † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Oedema peripheral † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Hepatobiliary disorders      
Cholangitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Hepatitis toxic † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Hepatotoxicity † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Hyperbilirubinaemia † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Portal hypertension † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Immune system disorders      
Hypersensitivity † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Infections and infestations      
Cellulitis † 1    
# participants affected / at risk     2/490 (0.41%)     3/488 (0.61%)  
Bacteraemia † 1    
# participants affected / at risk     1/490 (0.20%)     2/488 (0.41%)  
Device related infection † 1    
# participants affected / at risk     2/490 (0.41%)     1/488 (0.20%)  
Sepsis † 1    
# participants affected / at risk     2/490 (0.41%)     1/488 (0.20%)  
Urinary tract infection † 1    
# participants affected / at risk     3/490 (0.61%)     0/488 (0.00%)  
Clostridium difficile colitis † 1    
# participants affected / at risk     1/490 (0.20%)     1/488 (0.20%)  
Appendicitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Bronchitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Enterococcal infection † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Erysipelas † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Gastroenteritis norovirus † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
H1N1 influenza † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Herpes zoster † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Nasopharyngitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Parotitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Pneumonia † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Pneumonia bacterial † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Pyelonephritis acute † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Salmonellosis † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Staphylococcal sepsis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Tooth infection † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Injury, poisoning and procedural complications      
Femur fracture † 1    
# participants affected / at risk     2/490 (0.41%)     2/488 (0.41%)  
Ankle fracture † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Extradural haematoma † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Fall † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Femoral neck fracture † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Haemolytic transfusion reaction † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Hip fracture † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Infusion related reaction † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Open wound † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Subdural haemorrhage † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Wrist fracture † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Investigations      
Blood bilirubin increased † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Gamma-glutamyltransferase increased † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Metabolism and nutrition disorders      
Hyponatraemia † 1    
# participants affected / at risk     2/490 (0.41%)     1/488 (0.20%)  
Dehydration † 1    
# participants affected / at risk     0/490 (0.00%)     2/488 (0.41%)  
Failure to thrive † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Hypokalaemia † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     2/490 (0.41%)     0/488 (0.00%)  
Bone pain † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Muscular weakness † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Pain in extremity † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Pathological fracture † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Spinal column stenosis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Spondylitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Colon cancer † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Myelodysplastic syndrome † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     1/490 (0.20%)     2/488 (0.41%)  
Headache † 1    
# participants affected / at risk     1/490 (0.20%)     2/488 (0.41%)  
Cerebrovascular accident † 1    
# participants affected / at risk     1/490 (0.20%)     1/488 (0.20%)  
Coma † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Hydrocephalus † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Metabolic encephalopathy † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Parkinson's disease † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Status epilepticus † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Syncope † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Psychiatric disorders      
Confusional state † 1    
# participants affected / at risk     1/490 (0.20%)     1/488 (0.20%)  
Agitation † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Depression † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Renal and urinary disorders      
Dysuria † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Renal failure † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Ureteric obstruction † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Urinary tract obstruction † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Reproductive system and breast disorders      
Metrorrhagia † 1    
# participants affected / at risk     2/490 (0.41%)     1/488 (0.20%)  
Ovarian cyst † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Respiratory, thoracic and mediastinal disorders      
Pulmonary embolism † 1    
# participants affected / at risk     0/490 (0.00%)     7/488 (1.43%)  
Acute respiratory distress syndrome † 1    
# participants affected / at risk     1/490 (0.20%)     2/488 (0.41%)  
Pleural effusion † 1    
# participants affected / at risk     1/490 (0.20%)     1/488 (0.20%)  
Alveolitis allergic † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Asthma † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Haemoptysis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Hypoxia † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Pleuritic pain † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Pneumonitis † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Pulmonary oedema † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Respiratory failure † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Skin and subcutaneous tissue disorders      
Dermatitis contact † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Rash generalised † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Scar † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Skin haemorrhage † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Urticaria † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Surgical and medical procedures      
Platelet transfusion † 1    
# participants affected / at risk     1/490 (0.20%)     0/488 (0.00%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     0/490 (0.00%)     2/488 (0.41%)  
Jugular vein thrombosis † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Subclavian vein thrombosis † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Thrombosis † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Venous thrombosis † 1    
# participants affected / at risk     0/490 (0.00%)     1/488 (0.20%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.1




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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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