Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 3 for:    LUX-lung 5

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01466660
Recruitment Status : Completed
First Posted : November 8, 2011
Results First Posted : June 19, 2017
Last Update Posted : April 7, 2020
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

Two-arm, randomised (1:1 ratio), open-label, parallel group trial.

In the study disease response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

Pre-assignment Details All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal. 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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Period Title: Overall Study
Started 160 159
Completed 0 [1] 0 [1]
Not Completed 160 159
Reason Not Completed
Progressive Disease (RECIST 1.1)             120             127
Worsening of underlying cancer disease             5             2
Other adverse event             19             18
Protocol Violation             2             1
Refused continuation of trial medication             4             3
Other reason not defined above             10             8
[1]
On treatment at analysis cut-off date, 12 April 2019
Arm/Group Title Afatinib Gefitinib Total
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal. 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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal. 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%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 159 participants 319 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
94
  58.8%
88
  55.3%
182
  57.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.6%
0
   0.0%
1
   0.3%
White
48
  30.0%
54
  34.0%
102
  32.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
17
  10.6%
17
  10.7%
34
  10.7%
[1]
Measure Description: "Unknown or Not Reported" reflects the participants in France where race was not recorded.
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) defined as the time from date of randomisation to date of disease progression, or date of death if a patient died earlier. Participants with no event (Disease progression (PD) or death) were censored. PD was primarily evaluated for the primary analysis by an independent central imaging review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started, together with an absolute increase in the SoD of target lesions of at least 5 millimetre (mm) or the appearance of one or more new lesions. For the final analysis (analysis cut-off date 12 April 2019) status and date of PD were determined by investigator assessment.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set which included all patients randomised to receive treatment, whether treated or not.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 160 159
Median (95% Confidence Interval)
Unit of Measure: Months
12.78
(10.91 to 14.72)
11.17
(9.49 to 12.81)
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 (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0891
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 0.822
Confidence Interval (2-Sided) 95%
0.655 to 1.032
Estimation Comments A Cox proportional hazards model, stratified by EGFR mutation group and presence of baseline brain metastases was used to estimate the hazard ratio calculated as Afatinib divided by Gefitinib.
2.Primary Outcome
Title Time to Treatment Failure (TTF) (Main Overall Survival Analysis Cut-off Date, 08 April 2016)
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 1482 days
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set which included all patients randomised to receive treatment, whether treated or not.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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 (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0136
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 0.750
Confidence Interval (2-Sided) 95%
0.595 to 0.944
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. Participants for whom there is no evidence of death at the time of the analysis will be censored at the date that they were last known to be alive.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set which included all patients randomised to receive treatment, whether treated or not.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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 (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2343
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 0.862
Confidence Interval (2-Sided) 95%
0.674 to 1.101
Estimation Comments A Cox proportional hazards model, stratified by EGFR mutation group and presence of baseline brain metastases was used to estimate the hazard 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 best overall response of 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 version 1.1. for target lesions and assessed by Computed Tomography (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. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set which included all patients randomised to receive treatment, whether treated or not.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 160 159
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
79.4
(72.3 to 85.4)
74.8
(67.4 to 81.4)
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 (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3235
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 1.307
Confidence Interval (2-Sided) 95%
0.768 to 2.223
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 (best overall response of complete response or partial response) to study treatment 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. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the randomised set with objective response.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 127 119
Measure Type: Number
Unit of Measure: Participants
Week 4 81 74
Week 8 112 107
Week 16 119 117
Week 24 122 118
Week 32 125 118
Week 40 126 118
Week 48 127 119
6.Secondary Outcome
Title Duration of Objective Response
Hide Description Duration of objective response defined as the time of first objective response (best overall response of complete response or partial response) to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the randomised set with objective response.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 127 119
Median (95% Confidence Interval)
Unit of Measure: Months
11.86
(10.12 to 15.54)
11.07
(9.69 to 12.91)
7.Secondary Outcome
Title Disease Control
Hide Description Percentage of participants with disease control which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) 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 version 1.1. for target lesions and assessed by Computed Tomography (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; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Responses of SD were only considered if they occur ≥42 days from date of randomisation. For the final analysis (analysis cut-off date 12 April 2019) disease control was determined by investigator assessment.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set which included all patients randomised to receive treatment, whether treated or not.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 160 159
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
94.4
(89.6 to 97.4)
93.7
(88.7 to 96.9)
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 (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7856
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 1.138
Confidence Interval (2-Sided) 95%
0.447 to 2.896
Estimation Comments Ratio calculated as Afatinib divided by Gefitinib
8.Secondary Outcome
Title Duration of Disease Control
Hide Description Duration of disease control defined as the time from randomisation to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) the status and date of disease progression were determined by investigator assessment.
Time Frame From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the randomised set with disease control, that is, with best overall response of complete response or partial response or stable disease.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 151 149
Median (95% Confidence Interval)
Unit of Measure: Months
12.88
(11.14 to 14.88)
11.73
(10.58 to 14.55)
9.Secondary Outcome
Title Tumour Shrinkage (Main Overall Survival Analysis Cut-off Date, 08 April 2016)
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 1482 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the randomised set with tumour assessments.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 149 151
Least Squares Mean (95% Confidence Interval)
Unit of Measure: millimetre (mm)
34.79
(32.18 to 37.40)
38.25
(35.65 to 40.84)
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 (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0657
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 -3.45
Confidence Interval (2-Sided) 95%
-7.13 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.87
Estimation Comments Difference calculated as Afatinib minus Gefitinib
10.Secondary Outcome
Title Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015)
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
All randomised subjects with health-related quality of life data.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
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 (legacy)
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 (legacy)
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 (legacy)
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 2405 days. For All-Cause Mortality: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on death, up to 2465 days.
Adverse Event Reporting Description Treated set included all patients who were dispensed with and documented to have taken at least one dose of study medication. This set of patients was used for the evaluation of safety.
 
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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal. 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. Continuous daily dosing until disease progression, occurrence of unacceptable adverse events, or other reason necessitating withdrawal.
All-Cause Mortality
Afatinib Gefitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   126/160 (78.75%)   132/159 (83.02%) 
Hide Serious Adverse Events
Afatinib Gefitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   75/160 (46.88%)   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%) 
Haemorrhoids  1  0/160 (0.00%)  1/159 (0.63%) 
Pancreatitis  1  1/160 (0.63%)  0/159 (0.00%) 
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%) 
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%) 
Large intestine 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 haemorrhage  1  0/160 (0.00%)  1/159 (0.63%) 
Hip fracture  1  0/160 (0.00%)  1/159 (0.63%) 
Femur fracture  1  1/160 (0.63%)  0/159 (0.00%) 
Limb injury  1  1/160 (0.63%)  0/159 (0.00%) 
Skin laceration  1  1/160 (0.63%)  0/159 (0.00%) 
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%) 
Endometrial adenocarcinoma  1  1/160 (0.63%)  0/159 (0.00%) 
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%) 
Status epilepticus  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%)  5/159 (3.14%) 
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%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
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%)  11/159 (6.92%) 
Abdominal pain upper  1  17/160 (10.63%)  17/159 (10.69%) 
Constipation  1  29/160 (18.13%)  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%)  13/159 (8.18%) 
Mouth ulceration  1  20/160 (12.50%)  7/159 (4.40%) 
Nausea  1  43/160 (26.88%)  45/159 (28.30%) 
Stomatitis  1  63/160 (39.38%)  18/159 (11.32%) 
Vomiting  1  31/160 (19.38%)  19/159 (11.95%) 
General disorders     
Asthenia  1  21/160 (13.13%)  22/159 (13.84%) 
Chest pain  1  20/160 (12.50%)  19/159 (11.95%) 
Fatigue  1  34/160 (21.25%)  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  22/160 (13.75%)  10/159 (6.29%) 
Infections and infestations     
Conjunctivitis  1  14/160 (8.75%)  10/159 (6.29%) 
Folliculitis  1  10/160 (6.25%)  4/159 (2.52%) 
Nasopharyngitis  1  11/160 (6.88%)  11/159 (6.92%) 
Paronychia  1  89/160 (55.63%)  28/159 (17.61%) 
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  18/160 (11.25%)  9/159 (5.66%) 
Metabolism and nutrition disorders     
Decreased appetite  1  45/160 (28.13%)  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  22/160 (13.75%)  32/159 (20.13%) 
Muscle spasms  1  13/160 (8.13%)  12/159 (7.55%) 
Musculoskeletal chest pain  1  9/160 (5.63%)  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%) 
Headache  1  14/160 (8.75%)  22/159 (13.84%) 
Psychiatric disorders     
Insomnia  1  13/160 (8.13%)  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  48/160 (30.00%)  47/159 (29.56%) 
Dysphonia  1  10/160 (6.25%)  5/159 (3.14%) 
Dyspnoea  1  34/160 (21.25%)  26/159 (16.35%) 
Epistaxis  1  30/160 (18.75%)  14/159 (8.81%) 
Haemoptysis  1  5/160 (3.13%)  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  23/160 (14.37%)  6/159 (3.77%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
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 7, 2020