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Trial record 1 of 1 for:    NCT01466660
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LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung

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ClinicalTrials.gov Identifier: NCT01466660
Recruitment Status : Completed
First Posted : November 8, 2011
Results First Posted : June 19, 2017
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lung Neoplasms
Interventions Drug: Afatinib
Drug: gefitinib
Enrollment 319
Recruitment Details  
Pre-assignment Details In the study disease response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description Afatinib film-coated tablets administered orally, once daily. Starting dose was 40 milligram (mg), dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Period Title: Overall Study
Started 160 159
Completed 14 [1] 8 [1]
Not Completed 146 151
Reason Not Completed
Progressive Disease (RECIST 1.1)             115             122
Worsening of underlying cancer disease             5             2
Other adverse event             18             17
Protocol Violation             1             1
Refused continuation of trial medication             4             3
Other reason not defined above             3             6
[1]
On treatment at analysis cut-off date, 08 April 2016
Arm/Group Title Afatinib Gefitinib Total
Hide Arm/Group Description Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events. Total of all reporting groups
Overall Number of Baseline Participants 160 159 319
Hide Baseline Analysis Population Description
Randomised set which included all patients randomised to receive treatment, whether treated or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 160 participants 159 participants 319 participants
61.7  (11.5) 63.0  (10.4) 62.4  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 159 participants 319 participants
Female
91
  56.9%
106
  66.7%
197
  61.8%
Male
69
  43.1%
53
  33.3%
122
  38.2%
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) defined as the time from the date of randomisation to the date of disease progression, or to date of death if a patient died earlier. Disease progression was primarily evaluated by an independent central imaging review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 160 159
Median (95% Confidence Interval)
Unit of Measure: Months
11.04
(10.61 to 12.91)
10.94
(9.07 to 11.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments Exploratory trial, no formal hypotheses were tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0165
Comments p-value was not adjusted for multiple comparisons
Method Log Rank
Comments Stratified by Epidermal Growth Factor Receptor (EGFR) mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.732
Confidence Interval (2-Sided) 95%
0.566 to 0.947
Estimation Comments Ratio calculated as Afatinib divided by Gefitinib
2.Primary Outcome
Title Time to Treatment Failure (TTF)
Hide Description Time to Treatment Failure (TTF) which was the time from the date of randomisation to the date of i.e. permanent treatment discontinuation for any reason.
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 160 159
Median (95% Confidence Interval)
Unit of Measure: Months
13.67
(11.89 to 14.95)
11.53
(10.09 to 13.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments Exploratory trial, no formal hypotheses were tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0073
Comments p-value was not adjusted for multiple comparisons
Method Log Rank
Comments Stratified by EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.728
Confidence Interval (2-Sided) 95%
0.576 to 0.920
Estimation Comments Ratio calculated as Afatinib divided by Gefitinib
3.Primary Outcome
Title Overall Survival
Hide Description Overall survival (OS) which was defined as the time from the date of randomisation to the date of death.
Time Frame From first drug administration until last drug administration, up to 1482 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 160 159
Median (95% Confidence Interval)
Unit of Measure: Months
27.86
(25.13 to 32.85)
24.54
(20.57 to 28.88)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments Exploratory trial, no formal hypotheses were tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2580
Comments p-value was not adjusted for multiple comparisons
Method Log Rank
Comments Stratified by EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.860
Confidence Interval (2-Sided) 95%
0.662 to 1.117
Estimation Comments Ratio calculated as Afatinib divided by Gefitinib
4.Secondary Outcome
Title Objective Response Rate
Hide Description Objective response rate (ORR) which was defined as the number of participants with complete response (CR) or partial response (PR) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST v1.1. for target lesions and assessed by CT-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions from baseline; Overall Response (OR) = CR + PR
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 160 159
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
70.0
(62.3 to 77.0)
56.0
(47.9 to 63.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments Exploratory trial, no formal hypotheses were tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments p-value was not adjusted for multiple comparisons
Method Regression, Logistic
Comments Stratified for EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.873
Confidence Interval (2-Sided) 95%
1.176 to 2.985
Estimation Comments Ratio calculated as Afatinib divided by Gefitinib
5.Secondary Outcome
Title Time to Objective Response
Hide Description

Number of participants with objective response over time, cumulative number of participants is displayed.

Time to objective response was defined as the time from randomisation to the first recorded objective response.

Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set including patients with objective response
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 112 89
Measure Type: Number
Unit of Measure: Participants
Week 4 52 40
Week 8 77 63
Week 16 92 73
Week 24 99 81
Week 32 107 82
Week 40 110 85
Week 48 110 87
Week 56 111 88
Week 64 112 89
6.Secondary Outcome
Title Duration of Objective Response
Hide Description Duration of objective response defined as the time of first objective response to the time of progression or death, whichever occurred first (or date of censoring for progression free survival (PFS))
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set including patients with objective response
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 112 89
Median (95% Confidence Interval)
Unit of Measure: Months
10.09
(7.82 to 11.10)
8.38
(7.36 to 10.94)
7.Secondary Outcome
Title Disease Control
Hide Description Disease control which was defined as objective response (complete response or partial response) or stable disease (SD).
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 160 159
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
91.3
(85.8 to 95.1)
87.4
(81.2 to 92.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments Exploratory trial, no formal hypotheses were tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2372
Comments p-value was not adjusted for multiple comparisons
Method Regression, Logistic
Comments Stratified for EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.552
Confidence Interval (2-Sided) 95%
0.749 to 3.216
Estimation Comments Ratio calculated as Afatinib divided by Gefitinib
8.Secondary Outcome
Title Duration of Disease Control
Hide Description Duration of disease control was measured from randomisation to the time of progressive disease (PD) or death, whichever occurred first (or date of censoring for progression free survival (PFS))
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set including patients with disease control
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 146 139
Median (95% Confidence Interval)
Unit of Measure: Months
12.71
(10.94 to 14.59)
11.07
(10.84 to 12.81)
9.Secondary Outcome
Title Tumour Shrinkage
Hide Description Tumour shrinkage assessed by minimum sum of post-baseline target lesion diameters recorded after randomisation. A positive value shows a decrease in tumour size.
Time Frame From first drug administration until last drug administration, up to 1293 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set including patients with tumour assessments
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 149 151
Least Squares Mean (95% Confidence Interval)
Unit of Measure: millimetre (mm)
35.77
(33.18 to 38.37)
38.37
(35.79 to 40.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments Exploratory trial, no formal hypotheses were tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1637
Comments p-value was not adjusted for multiple comparisons
Method ANCOVA
Comments Adjusted for baseline sum of diameters, EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.59
Confidence Interval (2-Sided) 95%
-6.25 to 1.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.86
Estimation Comments Difference calculated as Afatinib minus Gefitinib
10.Secondary Outcome
Title Health-related Quality of Life
Hide Description

Health-related quality of life (HRQoL) measured using European Quality of life - 5 Dimensions (EQ-5D) score for United Kingdom (UK) and Belgium and European European Quality Visual Analogue Scale (EQ-VAS).

EQ-5D utility scores range from 0 (worst health) to 1 (full health).

EQ-VAS scores range from 0 (worst imaginable health state) to 100 (best imaginable health state).

Results display the mean score up to 56 weeks.

Time Frame Every 8 weeks, up to 56 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set including patients with available HRQoL data
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description:
Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events.
Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
Overall Number of Participants Analyzed 160 158
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
EQ-5D UK utility score
0.77
(0.75 to 0.80)
0.80
(0.77 to 0.82)
EQ-5D Belgium utility score
0.74
(0.72 to 0.77)
0.77
(0.75 to 0.80)
EQ-VAS utility score
74.5
(72.3 to 76.6)
76.0
(73.9 to 78.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments

EQ-5D UK utility score.

Exploratory trial, no formal hypotheses were tested.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1422
Comments p-value was not adjusted for multiple comparisons
Method Mixed Models Analysis
Comments Adjusted for EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.06 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.017
Estimation Comments Difference calculated as Afatinib minus Gefitinib
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments

EQ-5D Belgium utility score.

Exploratory trial, no formal hypotheses were tested.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0540
Comments p-value was not adjusted for multiple comparisons
Method Mixed Models Analysis
Comments Adjusted for EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.06 to 0.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.016
Estimation Comments Difference calculated as Afatinib divided by Gefitinib
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Afatinib, Gefitinib
Comments

EQ-VAS utility score.

Exploratory trial, no formal hypotheses were tested.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2032
Comments p-value was not adjusted for multiple comparisons
Method Mixed Models Analysis
Comments Adjusted for EGFR mutation group and presence of brain metastases at baseline
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.9 to 0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.21
Estimation Comments Difference calculated as Afatinib divided by Gefitinib
Time Frame From first drug administration until 28 days after last drug administration, up to 1510 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Afatinib Gefitinib
Hide Arm/Group Description Afatinib film-coated tablets administered orally, once daily. Starting dose was 40mg, dose escalation to 50mg was allowed after completing one 28-day treatment course, dose reduction to 40mg, 30mg or 20mg was required in the presence of protocol-defined adverse events. Gefitinib film-coated tablets, administered orally, once daily. Starting dose was 250mg, the investigator was allowed to modify dosing in the presence of drug-related adverse events.
All-Cause Mortality
Afatinib Gefitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Afatinib Gefitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   74/160 (46.25%)   64/159 (40.25%) 
Blood and lymphatic system disorders     
Anaemia  1  0/160 (0.00%)  1/159 (0.63%) 
Lymphoid tissue hyperplasia  1  1/160 (0.63%)  0/159 (0.00%) 
Bone marrow failure  1  0/160 (0.00%)  1/159 (0.63%) 
Cardiac disorders     
Acute coronary syndrome  1  1/160 (0.63%)  0/159 (0.00%) 
Angina pectoris  1  1/160 (0.63%)  0/159 (0.00%) 
Atrial fibrillation  1  0/160 (0.00%)  1/159 (0.63%) 
Coronary artery disease  1  1/160 (0.63%)  1/159 (0.63%) 
Myocardial infarction  1  2/160 (1.25%)  0/159 (0.00%) 
Pericardial effusion  1  1/160 (0.63%)  3/159 (1.89%) 
Coronary artery occlusion  1  0/160 (0.00%)  1/159 (0.63%) 
Ear and labyrinth disorders     
Sudden hearing loss  1  1/160 (0.63%)  0/159 (0.00%) 
Endocrine disorders     
Cushing's syndrome  1  1/160 (0.63%)  0/159 (0.00%) 
Eye disorders     
Macular degeneration  1  0/160 (0.00%)  1/159 (0.63%) 
Gastrointestinal disorders     
Abdominal pain  1  0/160 (0.00%)  1/159 (0.63%) 
Abdominal pain lower  1  0/160 (0.00%)  1/159 (0.63%) 
Anal haemorrhage  1  0/160 (0.00%)  1/159 (0.63%) 
Constipation  1  2/160 (1.25%)  0/159 (0.00%) 
Diarrhoea  1  11/160 (6.88%)  2/159 (1.26%) 
Gastrointestinal haemorrhage  1  0/160 (0.00%)  1/159 (0.63%) 
Ileus  1  1/160 (0.63%)  0/159 (0.00%) 
Intestinal obstruction  1  1/160 (0.63%)  0/159 (0.00%) 
Nausea  1  0/160 (0.00%)  1/159 (0.63%) 
Pancreatitis acute  1  1/160 (0.63%)  0/159 (0.00%) 
Stomatitis  1  3/160 (1.88%)  0/159 (0.00%) 
Vomiting  1  1/160 (0.63%)  3/159 (1.89%) 
General disorders     
Asthenia  1  4/160 (2.50%)  2/159 (1.26%) 
Chest pain  1  1/160 (0.63%)  0/159 (0.00%) 
Death  1  1/160 (0.63%)  0/159 (0.00%) 
Fatigue  1  0/160 (0.00%)  1/159 (0.63%) 
General physical health deterioration  1  1/160 (0.63%)  3/159 (1.89%) 
Pain  1  0/160 (0.00%)  2/159 (1.26%) 
Pyrexia  1  1/160 (0.63%)  0/159 (0.00%) 
Multiple organ dysfunction syndrome  1  1/160 (0.63%)  1/159 (0.63%) 
Hepatobiliary disorders     
Cholecystitis acute  1  1/160 (0.63%)  0/159 (0.00%) 
Cholelithiasis  1  1/160 (0.63%)  0/159 (0.00%) 
Hepatic failure  1  0/160 (0.00%)  1/159 (0.63%) 
Hepatic haemorrhage  1  1/160 (0.63%)  0/159 (0.00%) 
Hepatitis  1  0/160 (0.00%)  1/159 (0.63%) 
Infections and infestations     
Bronchitis  1  1/160 (0.63%)  0/159 (0.00%) 
Clostridium difficile colitis  1  1/160 (0.63%)  0/159 (0.00%) 
Empyema  1  1/160 (0.63%)  0/159 (0.00%) 
Encephalitis  1  1/160 (0.63%)  0/159 (0.00%) 
Erysipelas  1  1/160 (0.63%)  0/159 (0.00%) 
Gastroenteritis  1  1/160 (0.63%)  0/159 (0.00%) 
Infection  1  2/160 (1.25%)  1/159 (0.63%) 
Infectious colitis  1  1/160 (0.63%)  0/159 (0.00%) 
Influenza  1  1/160 (0.63%)  0/159 (0.00%) 
Lung infection  1  0/160 (0.00%)  1/159 (0.63%) 
Pneumonia  1  7/160 (4.38%)  5/159 (3.14%) 
Sepsis  1  1/160 (0.63%)  4/159 (2.52%) 
Skin bacterial infection  1  1/160 (0.63%)  0/159 (0.00%) 
Upper respiratory tract infection  1  2/160 (1.25%)  0/159 (0.00%) 
Urinary tract infection  1  0/160 (0.00%)  2/159 (1.26%) 
Urosepsis  1  1/160 (0.63%)  0/159 (0.00%) 
Lower respiratory tract infection  1  1/160 (0.63%)  0/159 (0.00%) 
Injury, poisoning and procedural complications     
Foreign body aspiration  1  1/160 (0.63%)  0/159 (0.00%) 
Lower limb fracture  1  1/160 (0.63%)  0/159 (0.00%) 
Spinal compression fracture  1  1/160 (0.63%)  0/159 (0.00%) 
Spinal fracture  1  1/160 (0.63%)  0/159 (0.00%) 
Thermal burn  1  1/160 (0.63%)  0/159 (0.00%) 
Wound  1  1/160 (0.63%)  0/159 (0.00%) 
Wound haemorrhage  1  0/160 (0.00%)  1/159 (0.63%) 
Hip fracture  1  0/160 (0.00%)  1/159 (0.63%) 
Investigations     
Blood sodium decreased  1  0/160 (0.00%)  1/159 (0.63%) 
Weight decreased  1  0/160 (0.00%)  1/159 (0.63%) 
Alanine aminotransferase increased  1  1/160 (0.63%)  0/159 (0.00%) 
Aspartate aminotransferase increased  1  1/160 (0.63%)  0/159 (0.00%) 
Blood bilirubin increased  1  1/160 (0.63%)  0/159 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/160 (0.00%)  1/159 (0.63%) 
Dehydration  1  3/160 (1.88%)  1/159 (0.63%) 
Hypokalaemia  1  1/160 (0.63%)  1/159 (0.63%) 
Hyponatraemia  1  1/160 (0.63%)  0/159 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  3/160 (1.88%)  2/159 (1.26%) 
Bone pain  1  1/160 (0.63%)  0/159 (0.00%) 
Intervertebral disc protrusion  1  1/160 (0.63%)  0/159 (0.00%) 
Muscular weakness  1  1/160 (0.63%)  1/159 (0.63%) 
Musculoskeletal pain  1  0/160 (0.00%)  2/159 (1.26%) 
Pain in extremity  1  0/160 (0.00%)  1/159 (0.63%) 
Spinal osteoarthritis  1  0/160 (0.00%)  1/159 (0.63%) 
Spinal pain  1  1/160 (0.63%)  0/159 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder transitional cell carcinoma  1  1/160 (0.63%)  0/159 (0.00%) 
Malignant neoplasm progression  1  7/160 (4.38%)  1/159 (0.63%) 
Metastases to central nervous system  1  0/160 (0.00%)  2/159 (1.26%) 
Metastases to meninges  1  1/160 (0.63%)  3/159 (1.89%) 
Renal cancer  1  0/160 (0.00%)  1/159 (0.63%) 
Small cell lung cancer  1  1/160 (0.63%)  0/159 (0.00%) 
Basal cell carcinoma  1  1/160 (0.63%)  0/159 (0.00%) 
Cancer pain  1  1/160 (0.63%)  1/159 (0.63%) 
Cholesteatoma  1  0/160 (0.00%)  1/159 (0.63%) 
Nervous system disorders     
Aphasia  1  0/160 (0.00%)  1/159 (0.63%) 
Cerebellar haemorrhage  1  0/160 (0.00%)  1/159 (0.63%) 
Cerebellar infarction  1  0/160 (0.00%)  1/159 (0.63%) 
Cerebral haemorrhage  1  0/160 (0.00%)  1/159 (0.63%) 
Cerebral infarction  1  1/160 (0.63%)  1/159 (0.63%) 
Cerebrovascular accident  1  1/160 (0.63%)  0/159 (0.00%) 
Cognitive disorder  1  0/160 (0.00%)  1/159 (0.63%) 
Dizziness  1  1/160 (0.63%)  5/159 (3.14%) 
Dystonia  1  1/160 (0.63%)  0/159 (0.00%) 
Embolic cerebral infarction  1  1/160 (0.63%)  0/159 (0.00%) 
Generalised tonic-clonic seizure  1  1/160 (0.63%)  0/159 (0.00%) 
Headache  1  1/160 (0.63%)  3/159 (1.89%) 
Hydrocephalus  1  0/160 (0.00%)  1/159 (0.63%) 
Ischaemic stroke  1  1/160 (0.63%)  1/159 (0.63%) 
Nervous system disorder  1  0/160 (0.00%)  1/159 (0.63%) 
Paraneoplastic encephalomyelitis  1  1/160 (0.63%)  0/159 (0.00%) 
Paraplegia  1  0/160 (0.00%)  1/159 (0.63%) 
Partial seizures  1  1/160 (0.63%)  0/159 (0.00%) 
Peripheral sensory neuropathy  1  1/160 (0.63%)  0/159 (0.00%) 
Seizure  1  0/160 (0.00%)  1/159 (0.63%) 
Spinal cord compression  1  1/160 (0.63%)  2/159 (1.26%) 
Cerebral disorder  1  0/160 (0.00%)  1/159 (0.63%) 
Cerebral ischaemia  1  0/160 (0.00%)  1/159 (0.63%) 
Dementia  1  1/160 (0.63%)  0/159 (0.00%) 
Psychiatric disorders     
Confusional state  1  2/160 (1.25%)  0/159 (0.00%) 
Depression  1  1/160 (0.63%)  0/159 (0.00%) 
Mental status changes  1  0/160 (0.00%)  1/159 (0.63%) 
Delirium  1  1/160 (0.63%)  1/159 (0.63%) 
Renal and urinary disorders     
Acute kidney injury  1  3/160 (1.88%)  0/159 (0.00%) 
Calculus bladder  1  0/160 (0.00%)  1/159 (0.63%) 
Renal colic  1  0/160 (0.00%)  1/159 (0.63%) 
Renal failure  1  0/160 (0.00%)  1/159 (0.63%) 
Urinary tract obstruction  1  1/160 (0.63%)  0/159 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/160 (0.00%)  1/159 (0.63%) 
Cervical dysplasia  1  0/160 (0.00%)  1/159 (0.63%) 
Pelvic pain  1  0/160 (0.00%)  1/159 (0.63%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/160 (0.63%)  1/159 (0.63%) 
Chronic obstructive pulmonary disease  1  1/160 (0.63%)  0/159 (0.00%) 
Cough  1  1/160 (0.63%)  0/159 (0.00%) 
Dyspnoea  1  2/160 (1.25%)  5/159 (3.14%) 
Haemoptysis  1  0/160 (0.00%)  2/159 (1.26%) 
Interstitial lung disease  1  1/160 (0.63%)  4/159 (2.52%) 
Pleural effusion  1  9/160 (5.63%)  2/159 (1.26%) 
Pleurisy  1  1/160 (0.63%)  0/159 (0.00%) 
Pneumonia aspiration  1  1/160 (0.63%)  1/159 (0.63%) 
Pneumothorax  1  3/160 (1.88%)  3/159 (1.89%) 
Pulmonary embolism  1  6/160 (3.75%)  4/159 (2.52%) 
Pulmonary oedema  1  1/160 (0.63%)  0/159 (0.00%) 
Respiratory distress  1  1/160 (0.63%)  0/159 (0.00%) 
Respiratory failure  1  1/160 (0.63%)  1/159 (0.63%) 
Skin and subcutaneous tissue disorders     
Eczema  1  1/160 (0.63%)  0/159 (0.00%) 
Intertrigo  1  1/160 (0.63%)  0/159 (0.00%) 
Pain of skin  1  1/160 (0.63%)  0/159 (0.00%) 
Seborrhoeic dermatitis  1  0/160 (0.00%)  1/159 (0.63%) 
Surgical and medical procedures     
Pneumonectomy  1  0/160 (0.00%)  1/159 (0.63%) 
Vascular disorders     
Deep vein thrombosis  1  1/160 (0.63%)  0/159 (0.00%) 
Hypertensive crisis  1  0/160 (0.00%)  1/159 (0.63%) 
Superior vena cava syndrome  1  1/160 (0.63%)  0/159 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Afatinib Gefitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   157/160 (98.13%)   159/159 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  14/160 (8.75%)  5/159 (3.14%) 
Eye disorders     
Dry eye  1  15/160 (9.38%)  13/159 (8.18%) 
Gastrointestinal disorders     
Abdominal pain  1  14/160 (8.75%)  9/159 (5.66%) 
Abdominal pain upper  1  15/160 (9.38%)  17/159 (10.69%) 
Constipation  1  27/160 (16.88%)  24/159 (15.09%) 
Diarrhoea  1  143/160 (89.38%)  102/159 (64.15%) 
Dry mouth  1  11/160 (6.88%)  14/159 (8.81%) 
Dyspepsia  1  16/160 (10.00%)  14/159 (8.81%) 
Gastrooesophageal reflux disease  1  6/160 (3.75%)  12/159 (7.55%) 
Mouth ulceration  1  20/160 (12.50%)  7/159 (4.40%) 
Nausea  1  42/160 (26.25%)  44/159 (27.67%) 
Stomatitis  1  63/160 (39.38%)  18/159 (11.32%) 
Vomiting  1  30/160 (18.75%)  19/159 (11.95%) 
General disorders     
Asthenia  1  21/160 (13.13%)  22/159 (13.84%) 
Chest pain  1  19/160 (11.88%)  16/159 (10.06%) 
Fatigue  1  32/160 (20.00%)  30/159 (18.87%) 
Influenza like illness  1  3/160 (1.88%)  8/159 (5.03%) 
Mucosal inflammation  1  32/160 (20.00%)  19/159 (11.95%) 
Oedema peripheral  1  11/160 (6.88%)  10/159 (6.29%) 
Pyrexia  1  21/160 (13.13%)  10/159 (6.29%) 
Infections and infestations     
Conjunctivitis  1  13/160 (8.13%)  10/159 (6.29%) 
Folliculitis  1  10/160 (6.25%)  4/159 (2.52%) 
Nasopharyngitis  1  10/160 (6.25%)  9/159 (5.66%) 
Paronychia  1  88/160 (55.00%)  27/159 (16.98%) 
Upper respiratory tract infection  1  16/160 (10.00%)  20/159 (12.58%) 
Urinary tract infection  1  18/160 (11.25%)  9/159 (5.66%) 
Investigations     
Alanine aminotransferase increased  1  19/160 (11.88%)  44/159 (27.67%) 
Aspartate aminotransferase increased  1  15/160 (9.38%)  38/159 (23.90%) 
Weight decreased  1  17/160 (10.63%)  9/159 (5.66%) 
Metabolism and nutrition disorders     
Decreased appetite  1  44/160 (27.50%)  39/159 (24.53%) 
Hypokalaemia  1  15/160 (9.38%)  7/159 (4.40%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  11/160 (6.88%)  16/159 (10.06%) 
Back pain  1  21/160 (13.13%)  31/159 (19.50%) 
Muscle spasms  1  13/160 (8.13%)  12/159 (7.55%) 
Musculoskeletal chest pain  1  8/160 (5.00%)  13/159 (8.18%) 
Musculoskeletal pain  1  14/160 (8.75%)  17/159 (10.69%) 
Neck pain  1  3/160 (1.88%)  12/159 (7.55%) 
Pain in extremity  1  20/160 (12.50%)  10/159 (6.29%) 
Nervous system disorders     
Dizziness  1  12/160 (7.50%)  18/159 (11.32%) 
Dysgeusia  1  11/160 (6.88%)  4/159 (2.52%) 
Headache  1  14/160 (8.75%)  22/159 (13.84%) 
Psychiatric disorders     
Insomnia  1  11/160 (6.88%)  9/159 (5.66%) 
Anxiety  1  4/160 (2.50%)  8/159 (5.03%) 
Renal and urinary disorders     
Dysuria  1  7/160 (4.38%)  9/159 (5.66%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  47/160 (29.38%)  47/159 (29.56%) 
Dysphonia  1  10/160 (6.25%)  5/159 (3.14%) 
Dyspnoea  1  33/160 (20.63%)  23/159 (14.47%) 
Epistaxis  1  30/160 (18.75%)  14/159 (8.81%) 
Haemoptysis  1  4/160 (2.50%)  9/159 (5.66%) 
Nasal dryness  1  12/160 (7.50%)  0/159 (0.00%) 
Nasal inflammation  1  11/160 (6.88%)  1/159 (0.63%) 
Oropharyngeal pain  1  7/160 (4.38%)  10/159 (6.29%) 
Productive cough  1  6/160 (3.75%)  11/159 (6.92%) 
Rhinorrhoea  1  24/160 (15.00%)  12/159 (7.55%) 
Skin and subcutaneous tissue disorders     
Acne  1  5/160 (3.13%)  17/159 (10.69%) 
Alopecia  1  19/160 (11.88%)  27/159 (16.98%) 
Dermatitis acneiform  1  34/160 (21.25%)  34/159 (21.38%) 
Dry skin  1  52/160 (32.50%)  63/159 (39.62%) 
Erythema  1  10/160 (6.25%)  4/159 (2.52%) 
Nail disorder  1  10/160 (6.25%)  3/159 (1.89%) 
Pruritus  1  40/160 (25.00%)  40/159 (25.16%) 
Rash  1  100/160 (62.50%)  87/159 (54.72%) 
Skin fissures  1  22/160 (13.75%)  6/159 (3.77%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01466660    
Other Study ID Numbers: 1200.123
2011-001814-33 ( EudraCT Number )
First Submitted: November 4, 2011
First Posted: November 8, 2011
Results First Submitted: April 4, 2017
Results First Posted: June 19, 2017
Last Update Posted: April 30, 2019