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Trial record 94 of 195 for:    Oral Cancer | ( Map: Mexico )

LUX-Head&Neck 1: A Phase III Trial of Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy

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ClinicalTrials.gov Identifier: NCT01345682
Recruitment Status : Completed
First Posted : May 2, 2011
Results First Posted : April 14, 2015
Last Update Posted : February 15, 2018
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
Conditions Head and Neck Neoplasms
Carcinoma, Squamous Cell
Interventions Drug: Afatinib
Drug: Methotrexate
Enrollment 483
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Period Title: Overall Study
Started 322 [1] 161 [1]
Completed 0 0
Not Completed 322 161
Reason Not Completed
Progressive disease per RECIST             226             93
Worsening of underlying cancer disease             23             12
Adverse Event             51             41
Non-compliance with protocol             0             1
Lost to Follow-up             0             1
Refused to continue trial medication             16             9
Not treated             2             1
Reason other than those specified above             4             3
[1]
Randomised
Arm/Group Title Afatinib (BIBW 2992) Methotrexate Total
Hide Arm/Group Description Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. Total of all reporting groups
Overall Number of Baseline Participants 322 161 483
Hide Baseline Analysis Population Description
The randomised set (RS) included all patients who were randomised to receive treatment, whether treated or not
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 322 participants 161 participants 483 participants
60.0  (8.8) 59.3  (9.7) 59.8  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 322 participants 161 participants 483 participants
Female
47
  14.6%
24
  14.9%
71
  14.7%
Male
275
  85.4%
137
  85.1%
412
  85.3%
1.Primary Outcome
Title Progression-free Survival (PFS) Based on Central Independent Review
Hide Description

PFS was defined as the time from the date of randomisation to disease progression or death, whichever occurred first. The primary analysis of PFS considered PFS events as assessed by central independent review, including all data collected until the study completion date (06 December 2016).

The date of disease progression was recorded based on RECIST version 1.1. Unequivocal progression of disease was determined if at least one of the following criteria applied:

  • At least 20% increase in the Sum of Diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm
  • Appearance of one or more new lesions
  • Unequivocal progression of existing non-target lesions
Time Frame From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set (RS)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Median (95% Confidence Interval)
Unit of Measure: months
2.63
(2.10 to 2.73)
1.74
(1.48 to 2.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0257
Comments Log−rank test stratified by baseline Eastern Cooperative Oncology Group (ECOG) Performance score (PS)(0 or 1) and prior use of Epidermal Growth Factor Receptor (EGFR)−targeted antibody in the Recurrent and/or Metastatic (R/M) setting (Yes or No).
Method Stratified Log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.792
Confidence Interval (2-Sided) 95%
0.643 to 0.977
Estimation Comments

Hazard ratio from Cox proportional hazards model stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).

Afatinib (BIBW 2992) vs Methotrexate

2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was a key secondary endpoint of this trial. OS was defined as the time from randomisation to death (irrespective of the cause of death). Patients for whom there was no evidence of death at the study completion date (06 December 2016) were to be censored on the date that they were last known to be alive.
Time Frame From randomization until death or study completion date (06Dec2016); Up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
RS
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Median (95% Confidence Interval)
Unit of Measure: months
6.87
(6.14 to 7.79)
6.01
(5.16 to 7.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6755
Comments Log−rank test stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).
Method Stratified Log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.958
Confidence Interval (2-Sided) 95%
0.786 to 1.169
Estimation Comments

Hazard ratio from Cox proportional hazards model stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).

Afatinib (BIBW 2992) vs Methotrexate

3.Secondary Outcome
Title Objective Response (OR)
Hide Description

OR is defined as the best overall response of complete response (CR) and partial response (PR) according to RECIST version 1.1, CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (<10mm short axis).

PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Other factors which add to the overall response of an imaging timepoint as PR are as below:-

  • CR in TL, but non-CR/Non-Progressive Disease (PD) in NTL leads to PR
  • CR in TL, but not evaluated NTL leads to PR
  • PR in TL, but non-PD NTL or not all evaluated NTL leads to PR;

All the above scenarios should also satisfy 'No occurrence of new lesions'.

Time Frame Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
RS
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.2
(7.16 to 14.09)
5.6
(2.58 to 10.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1010
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
0.88 to 4.14
Estimation Comments

Odds ratio, 95% Confidence Interval (CI) and p−value (two−sided) from logistic regression stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).

Afatinib (BIBW 2992) vs Methotrexate

4.Secondary Outcome
Title Disease Control (DC)
Hide Description

DC is defined as the best overall response of CR, PR, stable disease (SD) and non-CR/non-PD.

CR for target lesions (TL): Disappearance of all target lesions. CR for non-target lesions (NTL): Disappearance of all non-target lesions . All lymph nodes must be non-pathological in size (<10mm short axis).

PR for TL: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Other factors which add to the overall response of an imaging timepoint as PR are as below:-

  • CR in TL, but non-CR/Non-PD in NTL leads to PR
  • CR in TL, but not evaluated NTL leads to PR
  • PR in TL, but non-PD NTL or not all evaluated NTL leads to PR;

SD for TL: change in the sum of diameters does not satisfy PR or PD.

SD in TL, non-PD in NTL lead to overall response of SD, provided there is no appearance of new lesions.

Time Frame Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
RS
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
49.1
(43.48 to 54.67)
38.5
(30.95 to 46.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0353
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
1.03 to 2.26
Estimation Comments

Odds ratio, 95% CI and p−value (two−sided) from logistic regression stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).

Afatinib (BIBW 2992) vs Methotrexate

5.Secondary Outcome
Title Tumour Shrinkage
Hide Description

Tumour shrinkage, defined as the maximum decrease from baseline in the sum of diameters of the target lesions, as measured by central imaging. The longest diameter of target lesions was recorded, except for lymph nodes, which were measured by their short axis.

Negative values indicate a reduction in the sum of target lesion diameters and positive values an increase.

Percentage of Participants with Tumour shrinkage as per the categories (>=20% increase, >=0 − <20% increase, >0 − <30% decrease, >=30 − <50% decrease, >=50% decrease) are presented.

Time Frame Tumour imaging was to be performed every 6 weeks during the first 24 weeks of treatment, and hereafter every 8 weeks (data cut-off 07May2014); Up to 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 248 121
Measure Type: Number
Unit of Measure: percentage of participants
>=20% increase 16.5 21.1
>=0 − <20% increase 24.2 31.1
>0 − <30% decrease 23.6 16.1
>=30 − <50% decrease 6.2 4.3
>=50% decrease 5.0 1.9
6.Secondary Outcome
Title Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time
Hide Description

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35:

Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30.

Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30.

The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome.

Changes in scores over time were assessed using longitudinal models.

The analyses of HRQOL are presented for the 07 May 2014 cut-off date.

Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 265 117
Mean (Standard Error)
Unit of Measure: scores on a scale
11.8  (3.16) 16.2  (3.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments Changes in scores over time were assessed using longitudinal models, i.e. mixed effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score (PS) and prior use of EGFR-targeted antibody for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0300
Comments Adjusted for baseline ECOG performance score (0 or 1) and prior use of EGFR−targeted antibody for R/M HNSCC (Yes or No).
Method longitudinal models
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -4.4
Confidence Interval (2-Sided) 95%
-8.31 to -0.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.01
Estimation Comments Afatinib (BIBW 2992) vs Methotrexate
7.Secondary Outcome
Title Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time
Hide Description

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35:

Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30.

Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30.

The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome.

Changes in scores over time were assessed using longitudinal models.

The analyses of HRQOL are presented for the 07 May 2014 cut-off date.

Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 257 112
Mean (Standard Error)
Unit of Measure: scores on a scale
20.0  (3.40) 20.1  (3.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments Changes in scores over time were assessed using longitudinal models, i.e. mixed effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG PS and prior use of EGFR-targeted antibody for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9773
Comments Adjusted for baseline ECOG performance score (0 or 1) and prior use of EGFR−targeted antibody for R/M HNSCC (Yes or No).
Method longitudinal models
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-4.30 to 4.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.16
Estimation Comments Afatinib (BIBW 2992) vs Methotrexate
8.Secondary Outcome
Title Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time
Hide Description

The HRQOL analyses focused on pain, swallowing, and global health status measured by the European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaires Core 30 [QLQ-C30], and head and neck cancer specific supplementary module EORTC QLQ-H&N35:

Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30.

Pain scale includes items 31-34 from H&N 35; Swallowing scale includes items 35-38 from H&N35 and Global health status/QoL scale includes items 29-30 from C30.

The scores of these scales were averaged from the scores of the component items, transformed and analyzed on 0 - 100 scale. For pain and swallowing scales, higher scores represent worse outcome; for the global health/QoL scale, higher scores represent better outcome.

Changes in scores over time were assessed using longitudinal models.

The analyses of HRQOL are presented for the 07 May 2014 cut-off date.

Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 267 117
Mean (Standard Error)
Unit of Measure: scores on a scale
28.7  (3.54) 28.2  (3.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments Changes in scores over time were assessed using longitudinal models, i.e. mixed effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG PS and prior use of EGFR-targeted antibody for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7767
Comments Adjusted for baseline ECOG performance score (0 or 1) and prior use of EGFR−targeted antibody for R/M HNSCC (Yes or No).
Method longitudinal models
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-3.28 to 4.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.95
Estimation Comments Afatinib (BIBW 2992) vs Methotrexate
9.Secondary Outcome
Title Status Change in Pain Scale
Hide Description Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 265 117
Measure Type: Number
Unit of Measure: percentage of participants
Improved 26.4 23.1
Stable 32.1 31.6
Worsened 41.5 45.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.717 to 1.990
Estimation Comments Odds ratio, 95% CI and p−value (two−sided) from logistic regression stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No). Afatinib (BIBW 2992) vs Methotrexate
10.Secondary Outcome
Title Status Change in Swallowing Scale
Hide Description Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 257 112
Measure Type: Number
Unit of Measure: percentage of participants
Improved 26.1 23.2
Stable 34.2 29.5
Worsened 39.7 47.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.584
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.687 to 1.950
Estimation Comments Odds ratio, 95% CI and p−value (two−sided) from logistic regression stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No). Afatinib (BIBW 2992) vs Methotrexate
11.Secondary Outcome
Title Status Change in Global Health Status Scale
Hide Description Distribution of patients with improved, stable or worsened HRQOL: Improvement was defined as a score improved by at least 10 points from baseline (on the 0-100 point scale) at any time during the trial. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the trial. Otherwise, a patient was considered as stable.
Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS (Only patients with observed cases (OC) values were analysed)
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 267 117
Measure Type: Number
Unit of Measure: percentage of participants
Improved 30.3 29.1
Stable 26.6 25.6
Worsened 43.1 45.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.816
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.657 to 1.705
Estimation Comments Odds ratio, 95% CI and p−value (two−sided) from logistic regression stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No). Afatinib (BIBW 2992) vs Methotrexate
12.Secondary Outcome
Title Time to Deterioration in Pain
Hide Description The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Median (95% Confidence Interval)
Unit of Measure: months
3.02
(2.83 to 3.75)
2.30
(1.64 to 3.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0217
Comments Log−rank test stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).
Method Stratified Log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.55 to 0.96
Estimation Comments Hazard ratio from Cox proportional hazards model stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).
13.Secondary Outcome
Title Time to Deterioration in Swallowing
Hide Description The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Median (95% Confidence Interval)
Unit of Measure: months
3.75
(2.83 to 4.30)
2.10
(1.48 to 3.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0040
Comments Log−rank test stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).
Method Stratified Log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.50 to 0.89
Estimation Comments

Hazard ratio from Cox proportional hazards model stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).

Afatinib (BIBW 2992) vs Methotrexate

14.Secondary Outcome
Title Time to Deterioration in Global Health Status
Hide Description The time to deterioration was defined as the time from randomisation to a score decreased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.
Time Frame From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description:
Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Intravenous bolus injection of Methotrexate Starting dose 40 mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
Overall Number of Participants Analyzed 322 161
Median (95% Confidence Interval)
Unit of Measure: months
3.25
(2.83 to 4.01)
2.69
(1.61 to 2.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Methotrexate
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0268
Comments Log−rank test stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).
Method Stratified Log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.56 to 0.97
Estimation Comments

Hazard ratio from Cox proportional hazards model stratified by baseline ECOG PS (0 or 1) and prior use of EGFR−targeted antibody in the R/M setting (Yes or No).

Afatinib (BIBW 2992) vs Methotrexate

Time Frame From first administration of study medication (afatinib or methotrexate) and within 28 days after the last administration of study medication (study completion date is 06Dec2016); Up to 60 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Afatinib (BIBW 2992) Methotrexate
Hide Arm/Group Description Oral administration of Afatinib (film-coated tablets). Starting dose 40 milligram (mg) once daily; escalation to 50 mg/day and / or dose reduction to 40 mg/day (if applicable), 30 mg/day, or 20 mg/day (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction. Intravenous bolus injection of Methotrexate Starting dose 40 milligram per square meter mg/m² weekly; escalation to 50 mg/m² and / or dose reduction to 40 mg/m² (if applicable), 30 mg/m², and 20 mg/m² (according to the protocol-defined dose escalation and dose reduction scheme) if required. No dose increase was allowed after a dose reduction.
All-Cause Mortality
Afatinib (BIBW 2992) Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Afatinib (BIBW 2992) Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   168/320 (52.50%)   73/160 (45.63%) 
Blood and lymphatic system disorders     
Anaemia  1  3/320 (0.94%)  8/160 (5.00%) 
Febrile neutropenia  1  2/320 (0.63%)  2/160 (1.25%) 
Neutropenia  1  1/320 (0.31%)  3/160 (1.88%) 
Pancytopenia  1  0/320 (0.00%)  3/160 (1.88%) 
Thrombocytopenia  1  3/320 (0.94%)  1/160 (0.63%) 
Cardiac disorders     
Atrial fibrillation  1  0/320 (0.00%)  1/160 (0.63%) 
Atrial tachycardia  1  1/320 (0.31%)  0/160 (0.00%) 
Left ventricular dysfunction  1  1/320 (0.31%)  0/160 (0.00%) 
Myocardial infarction  1  0/320 (0.00%)  1/160 (0.63%) 
Tachycardia  1  1/320 (0.31%)  0/160 (0.00%) 
Congenital, familial and genetic disorders     
Tracheo-oesophageal fistula  1  3/320 (0.94%)  0/160 (0.00%) 
Eye disorders     
Blindness unilateral  1  1/320 (0.31%)  0/160 (0.00%) 
Keratitis  1  1/320 (0.31%)  0/160 (0.00%) 
Gastrointestinal disorders     
Colitis  1  1/320 (0.31%)  0/160 (0.00%) 
Diarrhoea  1  16/320 (5.00%)  1/160 (0.63%) 
Duodenal ulcer  1  1/320 (0.31%)  0/160 (0.00%) 
Dysphagia  1  9/320 (2.81%)  3/160 (1.88%) 
Gastric ulcer  1  1/320 (0.31%)  0/160 (0.00%) 
Gastrointestinal haemorrhage  1  1/320 (0.31%)  0/160 (0.00%) 
Gastrooesophageal reflux disease  1  1/320 (0.31%)  0/160 (0.00%) 
Haematemesis  1  1/320 (0.31%)  1/160 (0.63%) 
Intestinal obstruction  1  2/320 (0.63%)  0/160 (0.00%) 
Large intestine perforation  1  1/320 (0.31%)  0/160 (0.00%) 
Melaena  1  0/320 (0.00%)  1/160 (0.63%) 
Mouth haemorrhage  1  5/320 (1.56%)  0/160 (0.00%) 
Nausea  1  5/320 (1.56%)  1/160 (0.63%) 
Odynophagia  1  2/320 (0.63%)  0/160 (0.00%) 
Oesophageal fistula  1  1/320 (0.31%)  0/160 (0.00%) 
Oesophageal stenosis  1  1/320 (0.31%)  1/160 (0.63%) 
Retroperitoneal haemorrhage  1  0/320 (0.00%)  1/160 (0.63%) 
Stomatitis  1  3/320 (0.94%)  1/160 (0.63%) 
Vomiting  1  10/320 (3.13%)  1/160 (0.63%) 
General disorders     
Asthenia  1  6/320 (1.88%)  1/160 (0.63%) 
Complication associated with device  1  1/320 (0.31%)  0/160 (0.00%) 
Death  1  1/320 (0.31%)  1/160 (0.63%) 
Face oedema  1  1/320 (0.31%)  0/160 (0.00%) 
Facial pain  1  1/320 (0.31%)  0/160 (0.00%) 
Fatigue  1  3/320 (0.94%)  2/160 (1.25%) 
General physical health deterioration  1  27/320 (8.44%)  8/160 (5.00%) 
Hyperpyrexia  1  0/320 (0.00%)  1/160 (0.63%) 
Hyperthermia  1  1/320 (0.31%)  0/160 (0.00%) 
Mucosal haemorrhage  1  0/320 (0.00%)  1/160 (0.63%) 
Mucosal inflammation  1  3/320 (0.94%)  2/160 (1.25%) 
Multiple organ dysfunction syndrome  1  1/320 (0.31%)  1/160 (0.63%) 
Pain  1  2/320 (0.63%)  0/160 (0.00%) 
Pyrexia  1  7/320 (2.19%)  5/160 (3.13%) 
Sudden death  1  0/320 (0.00%)  1/160 (0.63%) 
Hepatobiliary disorders     
Hepatic failure  1  0/320 (0.00%)  1/160 (0.63%) 
Hepatic function abnormal  1  0/320 (0.00%)  1/160 (0.63%) 
Immune system disorders     
Drug hypersensitivity  1  0/320 (0.00%)  1/160 (0.63%) 
Infections and infestations     
Abscess oral  1  0/320 (0.00%)  1/160 (0.63%) 
Atypical pneumonia  1  0/320 (0.00%)  1/160 (0.63%) 
Bacteraemia  1  0/320 (0.00%)  1/160 (0.63%) 
Cellulitis  1  1/320 (0.31%)  0/160 (0.00%) 
Device related infection  1  4/320 (1.25%)  0/160 (0.00%) 
Empyema  1  1/320 (0.31%)  0/160 (0.00%) 
Infection  1  0/320 (0.00%)  1/160 (0.63%) 
Klebsiella sepsis  1  1/320 (0.31%)  0/160 (0.00%) 
Laryngitis  1  1/320 (0.31%)  0/160 (0.00%) 
Lower respiratory tract infection  1  1/320 (0.31%)  0/160 (0.00%) 
Lung infection  1  4/320 (1.25%)  2/160 (1.25%) 
Oral infection  1  1/320 (0.31%)  0/160 (0.00%) 
Otitis media  1  1/320 (0.31%)  0/160 (0.00%) 
Periorbital cellulitis  1  1/320 (0.31%)  0/160 (0.00%) 
Pneumonia  1  13/320 (4.06%)  3/160 (1.88%) 
Pulmonary sepsis  1  1/320 (0.31%)  0/160 (0.00%) 
Respiratory tract infection  1  4/320 (1.25%)  0/160 (0.00%) 
Sepsis  1  3/320 (0.94%)  2/160 (1.25%) 
Septic shock  1  2/320 (0.63%)  2/160 (1.25%) 
Skin infection  1  1/320 (0.31%)  0/160 (0.00%) 
Soft tissue infection  1  1/320 (0.31%)  0/160 (0.00%) 
Staphylococcal infection  1  1/320 (0.31%)  0/160 (0.00%) 
Staphylococcal sepsis  1  1/320 (0.31%)  0/160 (0.00%) 
Tracheitis  1  1/320 (0.31%)  1/160 (0.63%) 
Tracheobronchitis  1  3/320 (0.94%)  0/160 (0.00%) 
Urinary tract infection  1  1/320 (0.31%)  0/160 (0.00%) 
Wound sepsis  1  1/320 (0.31%)  0/160 (0.00%) 
Injury, poisoning and procedural complications     
Cervical vertebral fracture  1  0/320 (0.00%)  1/160 (0.63%) 
Contusion  1  0/320 (0.00%)  1/160 (0.63%) 
Fall  1  0/320 (0.00%)  1/160 (0.63%) 
Femur fracture  1  1/320 (0.31%)  0/160 (0.00%) 
Foreign body aspiration  1  0/320 (0.00%)  1/160 (0.63%) 
Poisoning deliberate  1  0/320 (0.00%)  1/160 (0.63%) 
Post procedural haemorrhage  1  3/320 (0.94%)  0/160 (0.00%) 
Tracheal haemorrhage  1  1/320 (0.31%)  0/160 (0.00%) 
Tracheal obstruction  1  0/320 (0.00%)  1/160 (0.63%) 
Vascular pseudoaneurysm  1  1/320 (0.31%)  0/160 (0.00%) 
Investigations     
Blood creatinine increased  1  2/320 (0.63%)  0/160 (0.00%) 
Blood pressure orthostatic decreased  1  1/320 (0.31%)  0/160 (0.00%) 
False positive investigation result  1  1/320 (0.31%)  0/160 (0.00%) 
International normalised ratio increased  1  1/320 (0.31%)  0/160 (0.00%) 
Oxygen saturation decreased  1  0/320 (0.00%)  1/160 (0.63%) 
Weight decreased  1  2/320 (0.63%)  2/160 (1.25%) 
Metabolism and nutrition disorders     
Cachexia  1  1/320 (0.31%)  2/160 (1.25%) 
Decreased appetite  1  7/320 (2.19%)  1/160 (0.63%) 
Dehydration  1  9/320 (2.81%)  1/160 (0.63%) 
Failure to thrive  1  0/320 (0.00%)  1/160 (0.63%) 
Food aversion  1  1/320 (0.31%)  0/160 (0.00%) 
Hypercalcaemia  1  3/320 (0.94%)  1/160 (0.63%) 
Hyperglycaemia  1  0/320 (0.00%)  1/160 (0.63%) 
Hypokalaemia  1  3/320 (0.94%)  1/160 (0.63%) 
Hyponatraemia  1  6/320 (1.88%)  1/160 (0.63%) 
Malnutrition  1  5/320 (1.56%)  1/160 (0.63%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/320 (0.63%)  0/160 (0.00%) 
Fistula  1  2/320 (0.63%)  0/160 (0.00%) 
Musculoskeletal chest pain  1  2/320 (0.63%)  0/160 (0.00%) 
Musculoskeletal pain  1  0/320 (0.00%)  1/160 (0.63%) 
Pain in extremity  1  2/320 (0.63%)  0/160 (0.00%) 
Rotator cuff syndrome  1  1/320 (0.31%)  0/160 (0.00%) 
Trismus  1  1/320 (0.31%)  0/160 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/320 (0.31%)  0/160 (0.00%) 
Infected neoplasm  1  1/320 (0.31%)  1/160 (0.63%) 
Laryngeal cancer  1  0/320 (0.00%)  1/160 (0.63%) 
Malignant neoplasm progression  1  40/320 (12.50%)  9/160 (5.63%) 
Metastases to liver  1  1/320 (0.31%)  0/160 (0.00%) 
Oesophageal squamous cell carcinoma  1  1/320 (0.31%)  0/160 (0.00%) 
Tumour associated fever  1  1/320 (0.31%)  0/160 (0.00%) 
Tumour haemorrhage  1  11/320 (3.44%)  4/160 (2.50%) 
Tumour pain  1  3/320 (0.94%)  2/160 (1.25%) 
Tumour ulceration  1  1/320 (0.31%)  0/160 (0.00%) 
Nervous system disorders     
Cerebrovascular accident  1  5/320 (1.56%)  0/160 (0.00%) 
Cognitive disorder  1  0/320 (0.00%)  1/160 (0.63%) 
Dizziness  1  1/320 (0.31%)  0/160 (0.00%) 
Epilepsy  1  1/320 (0.31%)  0/160 (0.00%) 
Generalised tonic-clonic seizure  1  1/320 (0.31%)  0/160 (0.00%) 
Headache  1  1/320 (0.31%)  0/160 (0.00%) 
Ischaemic stroke  1  1/320 (0.31%)  0/160 (0.00%) 
Paralysis recurrent laryngeal nerve  1  0/320 (0.00%)  1/160 (0.63%) 
Somnolence  1  1/320 (0.31%)  1/160 (0.63%) 
Spinal cord compression  1  1/320 (0.31%)  0/160 (0.00%) 
Syncope  1  2/320 (0.63%)  0/160 (0.00%) 
Product Issues     
Device dislocation  1  0/320 (0.00%)  1/160 (0.63%) 
Device leakage  1  1/320 (0.31%)  0/160 (0.00%) 
Psychiatric disorders     
Agitation  1  1/320 (0.31%)  0/160 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  3/320 (0.94%)  0/160 (0.00%) 
Renal failure  1  6/320 (1.88%)  1/160 (0.63%) 
Renal impairment  1  1/320 (0.31%)  0/160 (0.00%) 
Reproductive system and breast disorders     
Prostatomegaly  1  1/320 (0.31%)  0/160 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration  1  1/320 (0.31%)  1/160 (0.63%) 
Bronchial obstruction  1  2/320 (0.63%)  0/160 (0.00%) 
Bronchopneumopathy  1  1/320 (0.31%)  0/160 (0.00%) 
Dyspnoea  1  15/320 (4.69%)  4/160 (2.50%) 
Epistaxis  1  0/320 (0.00%)  2/160 (1.25%) 
Haemoptysis  1  4/320 (1.25%)  0/160 (0.00%) 
Hypoxia  1  1/320 (0.31%)  0/160 (0.00%) 
Increased bronchial secretion  1  0/320 (0.00%)  1/160 (0.63%) 
Laryngeal obstruction  1  1/320 (0.31%)  1/160 (0.63%) 
Laryngeal oedema  1  1/320 (0.31%)  2/160 (1.25%) 
Lung disorder  1  1/320 (0.31%)  1/160 (0.63%) 
Organising pneumonia  1  1/320 (0.31%)  1/160 (0.63%) 
Oropharyngeal pain  1  1/320 (0.31%)  0/160 (0.00%) 
Pharyngeal haemorrhage  1  1/320 (0.31%)  1/160 (0.63%) 
Pharyngeal stenosis  1  0/320 (0.00%)  1/160 (0.63%) 
Pleural effusion  1  4/320 (1.25%)  2/160 (1.25%) 
Pneumonia aspiration  1  3/320 (0.94%)  3/160 (1.88%) 
Pneumonitis  1  2/320 (0.63%)  3/160 (1.88%) 
Productive cough  1  1/320 (0.31%)  0/160 (0.00%) 
Pulmonary artery thrombosis  1  1/320 (0.31%)  0/160 (0.00%) 
Pulmonary embolism  1  1/320 (0.31%)  1/160 (0.63%) 
Pulmonary fibrosis  1  1/320 (0.31%)  0/160 (0.00%) 
Pulmonary haemorrhage  1  1/320 (0.31%)  0/160 (0.00%) 
Pulmonary hypertension  1  1/320 (0.31%)  0/160 (0.00%) 
Respiratory acidosis  1  0/320 (0.00%)  1/160 (0.63%) 
Respiratory depression  1  0/320 (0.00%)  1/160 (0.63%) 
Respiratory distress  1  4/320 (1.25%)  0/160 (0.00%) 
Respiratory failure  1  6/320 (1.88%)  1/160 (0.63%) 
Respiratory tract haemorrhage  1  1/320 (0.31%)  0/160 (0.00%) 
Stridor  1  2/320 (0.63%)  0/160 (0.00%) 
Skin and subcutaneous tissue disorders     
Palmar-plantar erythrodysaesthesia syndrome  1  1/320 (0.31%)  0/160 (0.00%) 
Skin haemorrhage  1  1/320 (0.31%)  0/160 (0.00%) 
Skin reaction  1  1/320 (0.31%)  0/160 (0.00%) 
Surgical and medical procedures     
Gastrostomy  1  1/320 (0.31%)  0/160 (0.00%) 
Vascular disorders     
Angiopathy  1  1/320 (0.31%)  0/160 (0.00%) 
Deep vein thrombosis  1  1/320 (0.31%)  1/160 (0.63%) 
Haemorrhage  1  0/320 (0.00%)  4/160 (2.50%) 
Hypotension  1  2/320 (0.63%)  0/160 (0.00%) 
Shock haemorrhagic  1  1/320 (0.31%)  0/160 (0.00%) 
Superior vena cava syndrome  1  0/320 (0.00%)  1/160 (0.63%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Afatinib (BIBW 2992) Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   309/320 (96.56%)   146/160 (91.25%) 
Blood and lymphatic system disorders     
Anaemia  1  61/320 (19.06%)  42/160 (26.25%) 
Leukopenia  1  3/320 (0.94%)  13/160 (8.13%) 
Neutropenia  1  1/320 (0.31%)  30/160 (18.75%) 
Thrombocytopenia  1  2/320 (0.63%)  10/160 (6.25%) 
Gastrointestinal disorders     
Abdominal pain  1  27/320 (8.44%)  5/160 (3.13%) 
Constipation  1  39/320 (12.19%)  28/160 (17.50%) 
Diarrhoea  1  239/320 (74.69%)  28/160 (17.50%) 
Dyspepsia  1  31/320 (9.69%)  4/160 (2.50%) 
Dysphagia  1  42/320 (13.13%)  12/160 (7.50%) 
Nausea  1  89/320 (27.81%)  43/160 (26.88%) 
Stomatitis  1  73/320 (22.81%)  28/160 (17.50%) 
Vomiting  1  63/320 (19.69%)  26/160 (16.25%) 
General disorders     
Asthenia  1  66/320 (20.63%)  41/160 (25.62%) 
Fatigue  1  72/320 (22.50%)  42/160 (26.25%) 
Mucosal inflammation  1  74/320 (23.13%)  42/160 (26.25%) 
Pyrexia  1  38/320 (11.88%)  27/160 (16.88%) 
Infections and infestations     
Conjunctivitis  1  25/320 (7.81%)  4/160 (2.50%) 
Folliculitis  1  24/320 (7.50%)  1/160 (0.63%) 
Paronychia  1  51/320 (15.94%)  0/160 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  4/320 (1.25%)  19/160 (11.88%) 
Aspartate aminotransferase increased  1  6/320 (1.88%)  20/160 (12.50%) 
Weight decreased  1  69/320 (21.56%)  25/160 (15.63%) 
Metabolism and nutrition disorders     
Decreased appetite  1  60/320 (18.75%)  39/160 (24.38%) 
Hypokalaemia  1  20/320 (6.25%)  10/160 (6.25%) 
Hyponatraemia  1  17/320 (5.31%)  4/160 (2.50%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  17/320 (5.31%)  5/160 (3.13%) 
Neck pain  1  17/320 (5.31%)  9/160 (5.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  25/320 (7.81%)  9/160 (5.63%) 
Nervous system disorders     
Headache  1  26/320 (8.13%)  16/160 (10.00%) 
Psychiatric disorders     
Anxiety  1  21/320 (6.56%)  7/160 (4.38%) 
Insomnia  1  27/320 (8.44%)  8/160 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  41/320 (12.81%)  23/160 (14.37%) 
Dyspnoea  1  45/320 (14.06%)  21/160 (13.13%) 
Epistaxis  1  32/320 (10.00%)  5/160 (3.13%) 
Skin and subcutaneous tissue disorders     
Acne  1  28/320 (8.75%)  2/160 (1.25%) 
Dermatitis acneiform  1  68/320 (21.25%)  4/160 (2.50%) 
Dry skin  1  47/320 (14.69%)  5/160 (3.13%) 
Palmar-plantar erythrodysaesthesia syndrome  1  19/320 (5.94%)  3/160 (1.88%) 
Pruritus  1  29/320 (9.06%)  1/160 (0.63%) 
Rash  1  134/320 (41.88%)  11/160 (6.88%) 
Skin fissures  1  40/320 (12.50%)  0/160 (0.00%) 
Vascular disorders     
Hypotension  1  9/320 (2.81%)  10/160 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01345682     History of Changes
Other Study ID Numbers: 1200.43
2011-000391-34 ( EudraCT Number: EudraCT )
First Submitted: April 28, 2011
First Posted: May 2, 2011
Results First Submitted: March 13, 2015
Results First Posted: April 14, 2015
Last Update Posted: February 15, 2018