Trial Outcomes & Findings for 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 (NCT NCT01345682)
NCT ID: NCT01345682
Last Updated: 2018-02-15
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
483 participants
Primary outcome timeframe
From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 months
Results posted on
2018-02-15
Participant Flow
Participant milestones
| Measure |
Afatinib (BIBW 2992)
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.
|
Methotrexate
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 Study
STARTED
|
322
|
161
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
322
|
161
|
Reasons for withdrawal
| Measure |
Afatinib (BIBW 2992)
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.
|
Methotrexate
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 Study
Progressive disease per RECIST
|
226
|
93
|
|
Overall Study
Worsening of underlying cancer disease
|
23
|
12
|
|
Overall Study
Adverse Event
|
51
|
41
|
|
Overall Study
Non-compliance with protocol
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Refused to continue trial medication
|
16
|
9
|
|
Overall Study
Not treated
|
2
|
1
|
|
Overall Study
Reason other than those specified above
|
4
|
3
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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
n=483 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.0 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
59.3 years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
59.8 years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
275 Participants
n=5 Participants
|
137 Participants
n=7 Participants
|
412 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From randomization until disease progression, death or study completion date (06Dec2016); Up to 60 monthsPopulation: Randomised set (RS)
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
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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.
|
|---|---|---|
|
Progression-free Survival (PFS) Based on Central Independent Review
|
2.63 months
Interval 2.1 to 2.73
|
1.74 months
Interval 1.48 to 2.4
|
SECONDARY outcome
Timeframe: From randomization until death or study completion date (06Dec2016); Up to 60 monthsPopulation: RS
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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 Survival (OS)
|
6.87 months
Interval 6.14 to 7.79
|
6.01 months
Interval 5.16 to 7.75
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: RS
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'.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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.
|
|---|---|---|
|
Objective Response (OR)
|
10.2 percentage of participants
Interval 7.16 to 14.09
|
5.6 percentage of participants
Interval 2.58 to 10.34
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: RS
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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.
|
|---|---|---|
|
Disease Control (DC)
|
49.1 percentage of participants
Interval 43.48 to 54.67
|
38.5 percentage of participants
Interval 30.95 to 46.49
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=248 Participants
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.
|
Methotrexate
n=121 Participants
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.
|
|---|---|---|
|
Tumour Shrinkage
>0 - <30% decrease
|
23.6 percentage of participants
|
16.1 percentage of participants
|
|
Tumour Shrinkage
>=20% increase
|
16.5 percentage of participants
|
21.1 percentage of participants
|
|
Tumour Shrinkage
>=0 - <20% increase
|
24.2 percentage of participants
|
31.1 percentage of participants
|
|
Tumour Shrinkage
>=30 - <50% decrease
|
6.2 percentage of participants
|
4.3 percentage of participants
|
|
Tumour Shrinkage
>=50% decrease
|
5.0 percentage of participants
|
1.9 percentage of participants
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=265 Participants
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.
|
Methotrexate
n=117 Participants
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.
|
|---|---|---|
|
Health Related Quality of Life (HRQOL)- Change in Pain Scores Over Time
|
11.8 scores on a scale
Standard Error 3.16
|
16.2 scores on a scale
Standard Error 3.43
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=257 Participants
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.
|
Methotrexate
n=112 Participants
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.
|
|---|---|---|
|
Health Related Quality of Life (HRQOL)- Change in Swallowing Scores Over Time
|
20.0 scores on a scale
Standard Error 3.40
|
20.1 scores on a scale
Standard Error 3.66
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=267 Participants
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.
|
Methotrexate
n=117 Participants
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.
|
|---|---|---|
|
Health Related Quality of Life (HRQOL)- Change in Global Health Scores Over Time
|
28.7 scores on a scale
Standard Error 3.54
|
28.2 scores on a scale
Standard Error 3.76
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=265 Participants
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.
|
Methotrexate
n=117 Participants
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.
|
|---|---|---|
|
Status Change in Pain Scale
Improved
|
26.4 percentage of participants
|
23.1 percentage of participants
|
|
Status Change in Pain Scale
Stable
|
32.1 percentage of participants
|
31.6 percentage of participants
|
|
Status Change in Pain Scale
Worsened
|
41.5 percentage of participants
|
45.3 percentage of participants
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=257 Participants
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.
|
Methotrexate
n=112 Participants
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.
|
|---|---|---|
|
Status Change in Swallowing Scale
Improved
|
26.1 percentage of participants
|
23.2 percentage of participants
|
|
Status Change in Swallowing Scale
Stable
|
34.2 percentage of participants
|
29.5 percentage of participants
|
|
Status Change in Swallowing Scale
Worsened
|
39.7 percentage of participants
|
47.3 percentage of participants
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=267 Participants
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.
|
Methotrexate
n=117 Participants
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.
|
|---|---|---|
|
Status Change in Global Health Status Scale
Improved
|
30.3 percentage of participants
|
29.1 percentage of participants
|
|
Status Change in Global Health Status Scale
Stable
|
26.6 percentage of participants
|
25.6 percentage of participants
|
|
Status Change in Global Health Status Scale
Worsened
|
43.1 percentage of participants
|
45.3 percentage of participants
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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.
|
|---|---|---|
|
Time to Deterioration in Pain
|
3.02 months
Interval 2.83 to 3.75
|
2.30 months
Interval 1.64 to 3.32
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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.
|
|---|---|---|
|
Time to Deterioration in Swallowing
|
3.75 months
Interval 2.83 to 4.3
|
2.10 months
Interval 1.48 to 3.32
|
SECONDARY outcome
Timeframe: From randomization until one month after discontinuation of study medication, death or data cut-off (07May2014); Up to 28 months.Population: RS
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.
Outcome measures
| Measure |
Afatinib (BIBW 2992)
n=322 Participants
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.
|
Methotrexate
n=161 Participants
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.
|
|---|---|---|
|
Time to Deterioration in Global Health Status
|
3.25 months
Interval 2.83 to 4.01
|
2.69 months
Interval 1.61 to 2.86
|
Adverse Events
Afatinib (BIBW 2992)
Serious events: 168 serious events
Other events: 309 other events
Deaths: 0 deaths
Methotrexate
Serious events: 73 serious events
Other events: 146 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Afatinib (BIBW 2992)
n=320 participants at risk
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.
|
Methotrexate
n=160 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.94%
3/320 • 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
|
5.0%
8/160 • 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
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.62%
2/320 • 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
|
1.2%
2/160 • 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
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.31%
1/320 • 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
|
1.9%
3/160 • 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
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/320 • 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
|
1.9%
3/160 • 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
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.94%
3/320 • 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
|
0.62%
1/160 • 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
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Cardiac disorders
Atrial tachycardia
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Cardiac disorders
Tachycardia
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
|
0.94%
3/320 • 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
|
0.00%
0/160 • 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
|
|
Eye disorders
Blindness unilateral
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Eye disorders
Keratitis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Colitis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Diarrhoea
|
5.0%
16/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Dysphagia
|
2.8%
9/320 • 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
|
1.9%
3/160 • 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
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Haematemesis
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
1.6%
5/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Nausea
|
1.6%
5/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Odynophagia
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Oesophageal fistula
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Stomatitis
|
0.94%
3/320 • 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
|
0.62%
1/160 • 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
|
|
Gastrointestinal disorders
Vomiting
|
3.1%
10/320 • 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
|
0.62%
1/160 • 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
|
|
General disorders
Asthenia
|
1.9%
6/320 • 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
|
0.62%
1/160 • 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
|
|
General disorders
Complication associated with device
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
General disorders
Death
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
General disorders
Face oedema
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
General disorders
Facial pain
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
General disorders
Fatigue
|
0.94%
3/320 • 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
|
1.2%
2/160 • 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
|
|
General disorders
General physical health deterioration
|
8.4%
27/320 • 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
|
5.0%
8/160 • 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
|
|
General disorders
Hyperpyrexia
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
General disorders
Hyperthermia
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
General disorders
Mucosal haemorrhage
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
General disorders
Mucosal inflammation
|
0.94%
3/320 • 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
|
1.2%
2/160 • 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
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
General disorders
Pain
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
General disorders
Pyrexia
|
2.2%
7/320 • 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
|
3.1%
5/160 • 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
|
|
General disorders
Sudden death
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Abscess oral
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Atypical pneumonia
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Cellulitis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Device related infection
|
1.2%
4/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Empyema
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Infection
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Klebsiella sepsis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Laryngitis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Lower respiratory tract infection
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Lung infection
|
1.2%
4/320 • 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
|
1.2%
2/160 • 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
|
|
Infections and infestations
Oral infection
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Otitis media
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Periorbital cellulitis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Pneumonia
|
4.1%
13/320 • 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
|
1.9%
3/160 • 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
|
|
Infections and infestations
Pulmonary sepsis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Respiratory tract infection
|
1.2%
4/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Sepsis
|
0.94%
3/320 • 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
|
1.2%
2/160 • 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
|
|
Infections and infestations
Septic shock
|
0.62%
2/320 • 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
|
1.2%
2/160 • 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
|
|
Infections and infestations
Skin infection
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Soft tissue infection
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Staphylococcal infection
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Staphylococcal sepsis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Tracheitis
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Tracheobronchitis
|
0.94%
3/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Urinary tract infection
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Infections and infestations
Wound sepsis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Injury, poisoning and procedural complications
Foreign body aspiration
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Injury, poisoning and procedural complications
Poisoning deliberate
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.94%
3/320 • 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
|
0.00%
0/160 • 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
|
|
Injury, poisoning and procedural complications
Tracheal haemorrhage
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Injury, poisoning and procedural complications
Tracheal obstruction
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Injury, poisoning and procedural complications
Vascular pseudoaneurysm
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Investigations
Blood creatinine increased
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Investigations
Blood pressure orthostatic decreased
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Investigations
False positive investigation result
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Investigations
International normalised ratio increased
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Investigations
Oxygen saturation decreased
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Investigations
Weight decreased
|
0.62%
2/320 • 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
|
1.2%
2/160 • 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
|
|
Metabolism and nutrition disorders
Cachexia
|
0.31%
1/320 • 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
|
1.2%
2/160 • 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
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.2%
7/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Dehydration
|
2.8%
9/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Food aversion
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.94%
3/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.94%
3/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.9%
6/320 • 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
|
0.62%
1/160 • 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
|
|
Metabolism and nutrition disorders
Malnutrition
|
1.6%
5/320 • 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
|
0.62%
1/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
12.5%
40/320 • 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
|
5.6%
9/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal squamous cell carcinoma
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
3.4%
11/320 • 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
|
2.5%
4/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.94%
3/320 • 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
|
1.2%
2/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour ulceration
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Cerebrovascular accident
|
1.6%
5/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Nervous system disorders
Dizziness
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Epilepsy
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Headache
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Ischaemic stroke
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Paralysis recurrent laryngeal nerve
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Nervous system disorders
Somnolence
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Nervous system disorders
Spinal cord compression
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Nervous system disorders
Syncope
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Product Issues
Device dislocation
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Product Issues
Device leakage
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Psychiatric disorders
Agitation
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Renal and urinary disorders
Acute kidney injury
|
0.94%
3/320 • 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
|
0.00%
0/160 • 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
|
|
Renal and urinary disorders
Renal failure
|
1.9%
6/320 • 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
|
0.62%
1/160 • 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
|
|
Renal and urinary disorders
Renal impairment
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopneumopathy
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.7%
15/320 • 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
|
2.5%
4/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/320 • 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
|
1.2%
2/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.2%
4/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Increased bronchial secretion
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal obstruction
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema
|
0.31%
1/320 • 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
|
1.2%
2/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal haemorrhage
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal stenosis
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.2%
4/320 • 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
|
1.2%
2/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.94%
3/320 • 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
|
1.9%
3/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.62%
2/320 • 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
|
1.9%
3/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory depression
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
1.2%
4/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.9%
6/320 • 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
|
0.62%
1/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Skin and subcutaneous tissue disorders
Skin reaction
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Surgical and medical procedures
Gastrostomy
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Vascular disorders
Angiopathy
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Vascular disorders
Deep vein thrombosis
|
0.31%
1/320 • 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
|
0.62%
1/160 • 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
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/320 • 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
|
2.5%
4/160 • 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
|
|
Vascular disorders
Hypotension
|
0.62%
2/320 • 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
|
0.00%
0/160 • 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
|
|
Vascular disorders
Shock haemorrhagic
|
0.31%
1/320 • 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
|
0.00%
0/160 • 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
|
|
Vascular disorders
Superior vena cava syndrome
|
0.00%
0/320 • 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
|
0.62%
1/160 • 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
|
Other adverse events
| Measure |
Afatinib (BIBW 2992)
n=320 participants at risk
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.
|
Methotrexate
n=160 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
19.1%
61/320 • 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
|
26.2%
42/160 • 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
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.94%
3/320 • 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
|
8.1%
13/160 • 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
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.31%
1/320 • 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
|
18.8%
30/160 • 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
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.62%
2/320 • 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
|
6.2%
10/160 • 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
|
|
Gastrointestinal disorders
Abdominal pain
|
8.4%
27/320 • 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
|
3.1%
5/160 • 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
|
|
Gastrointestinal disorders
Constipation
|
12.2%
39/320 • 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
|
17.5%
28/160 • 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
|
|
Gastrointestinal disorders
Diarrhoea
|
74.7%
239/320 • 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
|
17.5%
28/160 • 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
|
|
Gastrointestinal disorders
Dyspepsia
|
9.7%
31/320 • 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
|
2.5%
4/160 • 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
|
|
Gastrointestinal disorders
Dysphagia
|
13.1%
42/320 • 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
|
7.5%
12/160 • 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
|
|
Gastrointestinal disorders
Nausea
|
27.8%
89/320 • 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
|
26.9%
43/160 • 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
|
|
Gastrointestinal disorders
Stomatitis
|
22.8%
73/320 • 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
|
17.5%
28/160 • 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
|
|
Gastrointestinal disorders
Vomiting
|
19.7%
63/320 • 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
|
16.2%
26/160 • 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
|
|
General disorders
Asthenia
|
20.6%
66/320 • 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
|
25.6%
41/160 • 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
|
|
General disorders
Fatigue
|
22.5%
72/320 • 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
|
26.2%
42/160 • 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
|
|
General disorders
Mucosal inflammation
|
23.1%
74/320 • 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
|
26.2%
42/160 • 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
|
|
General disorders
Pyrexia
|
11.9%
38/320 • 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
|
16.9%
27/160 • 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
|
|
Infections and infestations
Conjunctivitis
|
7.8%
25/320 • 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
|
2.5%
4/160 • 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
|
|
Infections and infestations
Folliculitis
|
7.5%
24/320 • 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
|
0.62%
1/160 • 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
|
|
Infections and infestations
Paronychia
|
15.9%
51/320 • 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
|
0.00%
0/160 • 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
|
|
Investigations
Alanine aminotransferase increased
|
1.2%
4/320 • 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
|
11.9%
19/160 • 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
|
|
Investigations
Aspartate aminotransferase increased
|
1.9%
6/320 • 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
|
12.5%
20/160 • 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
|
|
Investigations
Weight decreased
|
21.6%
69/320 • 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
|
15.6%
25/160 • 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
|
|
Metabolism and nutrition disorders
Decreased appetite
|
18.8%
60/320 • 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
|
24.4%
39/160 • 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
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.2%
20/320 • 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
|
6.2%
10/160 • 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
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.3%
17/320 • 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
|
2.5%
4/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.3%
17/320 • 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
|
3.1%
5/160 • 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
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.3%
17/320 • 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
|
5.6%
9/160 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
7.8%
25/320 • 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
|
5.6%
9/160 • 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
|
|
Nervous system disorders
Headache
|
8.1%
26/320 • 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
|
10.0%
16/160 • 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
|
|
Psychiatric disorders
Anxiety
|
6.6%
21/320 • 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
|
4.4%
7/160 • 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
|
|
Psychiatric disorders
Insomnia
|
8.4%
27/320 • 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
|
5.0%
8/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.8%
41/320 • 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
|
14.4%
23/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.1%
45/320 • 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
|
13.1%
21/160 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.0%
32/320 • 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
|
3.1%
5/160 • 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
|
|
Skin and subcutaneous tissue disorders
Acne
|
8.8%
28/320 • 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
|
1.2%
2/160 • 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
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
21.2%
68/320 • 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
|
2.5%
4/160 • 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
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.7%
47/320 • 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
|
3.1%
5/160 • 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
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
5.9%
19/320 • 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
|
1.9%
3/160 • 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
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.1%
29/320 • 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
|
0.62%
1/160 • 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
|
|
Skin and subcutaneous tissue disorders
Rash
|
41.9%
134/320 • 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
|
6.9%
11/160 • 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
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
12.5%
40/320 • 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
|
0.00%
0/160 • 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
|
|
Vascular disorders
Hypotension
|
2.8%
9/320 • 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
|
6.2%
10/160 • 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
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER