Trial Outcomes & Findings for BIBW 2992 (Afatinib) in Head & Neck Cancer (NCT NCT00514943)
NCT ID: NCT00514943
Last Updated: 2016-07-26
Results Overview
Tumor shrinkage before crossover was defined as the change from baseline in the smallest post-randomisation sum of the longest diameters of target lesions (SLD), calculated as the smallest SLD after randomisation but before crossover minus SLD at baseline. Baseline was the SLD measured before randomisation. A negative value means the smallest post-randomisation SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline. Mean calculated is actually the Adjusted mean. Adjusted mean is obtained from fitting an ANCOVA model including treatment, stratification factor prior chemotherapy for recurrent/metastatic disease and the baseline sum of longest distance of target lesions as covariates.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
124 participants
Primary outcome timeframe
From randomization until start of Stage 2 treatment, or within 28 days after the termination of Stage 1.
Results posted on
2016-07-26
Participant Flow
Open-label randomized, cross-over study. 124 patients were randomised. 3 patients were not treated, 1 in Afatinib arm and 2 in Cetuximab arm.
Participant milestones
| Measure |
Afatinib 50 mg / Cetuximab 250mg/m2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
Cetuximab 250 mg/m2 / Afatinib 50 mg
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
|---|---|---|
|
Stage 1
STARTED
|
62
|
62
|
|
Stage 1
COMPLETED
|
32
|
36
|
|
Stage 1
NOT COMPLETED
|
30
|
26
|
|
Stage 2
STARTED
|
32
|
36
|
|
Stage 2
COMPLETED
|
0
|
0
|
|
Stage 2
NOT COMPLETED
|
32
|
36
|
Reasons for withdrawal
| Measure |
Afatinib 50 mg / Cetuximab 250mg/m2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
Cetuximab 250 mg/m2 / Afatinib 50 mg
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
|---|---|---|
|
Stage 1
Progressive disease
|
4
|
8
|
|
Stage 1
Other Adverse Event
|
16
|
6
|
|
Stage 1
Not treated
|
1
|
2
|
|
Stage 1
Patient refused to continue study meds
|
8
|
3
|
|
Stage 1
Other than stated above
|
1
|
7
|
|
Stage 2
Progressive disease
|
27
|
24
|
|
Stage 2
Other Adverse Event
|
3
|
10
|
|
Stage 2
Patient refused to continue study meds
|
2
|
0
|
|
Stage 2
Other than stated above
|
0
|
2
|
Baseline Characteristics
BIBW 2992 (Afatinib) in Head & Neck Cancer
Baseline characteristics by cohort
| Measure |
Afatinib 50 mg / Cetuximab 250mg/m2
n=62 Participants
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
Cetuximab 250 mg/m2 / Afatinib 50 mg
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
58.8 years
STANDARD_DEVIATION 8.7 • n=7 Participants
|
58.3 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Prior chemotherapies (CT)for recurrent/metastatic disease (R/M)
Yes
|
42 Number of participants
n=5 Participants
|
41 Number of participants
n=7 Participants
|
83 Number of participants
n=5 Participants
|
|
Prior chemotherapies (CT)for recurrent/metastatic disease (R/M)
No
|
20 Number of participants
n=5 Participants
|
21 Number of participants
n=7 Participants
|
41 Number of participants
n=5 Participants
|
|
Baseline sum of longest diameters (SLD) of target lesions by investigator assessments
|
71.4 millimeters
STANDARD_DEVIATION 44.6 • n=5 Participants
|
65.4 millimeters
STANDARD_DEVIATION 44.2 • n=7 Participants
|
68.4 millimeters
STANDARD_DEVIATION 44.3 • n=5 Participants
|
PRIMARY outcome
Timeframe: From randomization until start of Stage 2 treatment, or within 28 days after the termination of Stage 1.Population: Randomised Set (RS). The randomised set includes all patients who were randomised to receive treatment, whether treated or not. However, patients without baseline or post-baseline tumor measurements were excluded.
Tumor shrinkage before crossover was defined as the change from baseline in the smallest post-randomisation sum of the longest diameters of target lesions (SLD), calculated as the smallest SLD after randomisation but before crossover minus SLD at baseline. Baseline was the SLD measured before randomisation. A negative value means the smallest post-randomisation SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline. Mean calculated is actually the Adjusted mean. Adjusted mean is obtained from fitting an ANCOVA model including treatment, stratification factor prior chemotherapy for recurrent/metastatic disease and the baseline sum of longest distance of target lesions as covariates.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=50 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=55 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Tumor Shrinkage Before Crossover (Stage 1) of the Trial as Per Investigator Assessment
|
-3.86 millimeter
Standard Error 3.62
|
-2.37 millimeter
Standard Error 3.47
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline assessed prior to first dose of Stage 2 study medication to 28 days after termination of Stage 2 treatment.Population: Patients treated in stage 2 : This analysis set included all patients who received treatment: 36 patients in the afatinib and 32 patients in the cetuximab arm.
Tumor shrinkage after crossover was defined as the change from baseline in the smallest post-crossover sum of the longest diameters of target lesions (SLD), calculated as the smallest SLD after crossover minus SLD at baseline. Baseline was the SLD measured at the time of crossover, or the closest measurement before the patient started stage 2 treatment. A negative value means the smallest post-crossover SLD was smaller than baseline (decreased after crossover), a positive value means tumor size increased after crossover.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=29 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=27 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Tumor Shrinkage After Crossover (Stage 2) as Per Investigator Assessments
|
2 millimeters
Standard Deviation 15
|
16 millimeters
Standard Deviation 30
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatmentPopulation: Randomised set (RS).
Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Objective response ( complete response (CR) or partial response (PR)) assessed by the investigator according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Disease control (CR, PR, SD)
|
31 Number of participants
|
35 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Objective response (CR, PR)
|
10 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Complete response (CR)
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Partial response (PR)
|
10 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Stable disease (SD)
|
21 Number of participants
|
31 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Progressive disease (PD)
|
16 Number of participants
|
19 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Not evaluable
|
5 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Missing
|
10 Number of participants
|
7 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatmentPopulation: Randomised set (RS).
Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Best objective response ( complete response (CR) or partial response (PR)) as assessed by the independent central review (ICR) according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Complete response (CR)
|
0 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Partial response (PR)
|
5 Number of participants
|
6 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Disease control (CR, PR, SD)
|
29 Number of participants
|
30 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Objective response (CR,PR)
|
5 Number of participants
|
6 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Stable disease (SD)
|
24 Number of participants
|
24 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Progressive disease (PD)
|
21 Number of participants
|
21 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Not evaluable
|
2 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
Missing
|
10 Number of participants
|
8 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatmentPopulation: Patients treated in Stage 2
Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Objective response ( complete response (CR) or partial response (PR)) assessed by the investigator according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=36 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=32 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Disease control (CR, PR, SD)
|
14 Number of participants
|
6 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Objective response (CR,PR)
|
1 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Complete response (CR)
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Partial response (PR)
|
0 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Stable disease (SD)
|
13 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Progressive disease (PD)
|
16 Number of participants
|
20 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Not evaluable
|
1 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Missing
|
5 Number of participants
|
2 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatmentPopulation: Patients treated in Stage 2
Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Best objective response ( complete response (CR) or partial response (PR)) as assessed by the independent central review (ICR) according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=36 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=32 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Disease control (CR, PR, SD)
|
12 Number of participants
|
6 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Objective response
|
0 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Complete response (CR)
|
0 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Partial response (PR)
|
0 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Stable disease (SD)
|
12 Number of participants
|
6 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Progressive disease (PD)
|
18 Number of participants
|
21 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Not evaluable
|
1 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
Missing
|
5 Number of participants
|
1 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatmentPopulation: Randomised set (RS).
Best RECIST Assessment as onset of confirmed objective response as per Investigator assessment for Stage 1.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=10 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=4 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1
Week 8 (Day 43 - 84)
|
1 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1
Week 4 (Day 1 - 42)
|
3 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1
Week 16 (Day 85 - 140)
|
4 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1
Week 24 (Day 141 - 196)
|
2 Number of participants
|
0 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatmentPopulation: Randomised set (RS).
Best RECIST Assessment as onset of confirmed objective response as per the independent central review (ICR) according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=5 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=6 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1
Week 4 (Day 1 - 42)
|
1 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1
Week 8 (Day 43 - 84)
|
2 Number of participants
|
3 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1
Week 16 (Day 85 - 140)
|
2 Number of participants
|
2 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1
Week 24 (Day 141 - 196)
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatmentPopulation: Patients treated in Stage 2
Best RECIST Assessment as onset of confirmed objective response as per Investigator assessment according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=1 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=2 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 2
Week 2 (Day 1 - 14)
|
0 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 2
Week 4 (Day 15 - 56)
|
1 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 2
Week 12 (Day 57 - 112)
|
0 Number of participants
|
1 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatmentPopulation: Randomised Set (RS)
Best RECIST Assessment as duration of confirmed objective response and disease control as per Investigator assessment according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 1
Duration of objective response (N=10; N=4)
|
21.4 Weeks
Standard Deviation 12.2
|
58.9 Weeks
Standard Deviation 98.1
|
—
|
—
|
|
Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 1
Duration of disease control(N=31; N=35)
|
25.1 Weeks
Standard Deviation 13.9
|
30.3 Weeks
Standard Deviation 35.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatmentPopulation: Randomised Set (RS)
Best RECIST Assessment as duration of confirmed objective response and disease control as per the independent central review (ICR) according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Confirmed Duration of Confirmed Objective Response and Disease Control as Per ICR for Stage 1
Duration of objective response (N=5; N=6)
|
28.0 Weeks
Standard Deviation 12.6
|
55.1 Weeks
Standard Deviation 76.6
|
—
|
—
|
|
Best RECIST Assessment as Confirmed Duration of Confirmed Objective Response and Disease Control as Per ICR for Stage 1
Duration of disease control(N=29; N=30)
|
22.8 Weeks
Standard Deviation 11.0
|
28.8 Weeks
Standard Deviation 38.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatmentPopulation: patients treated in stage 2
Best RECIST Assessment as confirmed duration of objective response and disease control as per Investigator assessment according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=36 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=32 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 2
Duration of objective response (N=1; N=2)
|
24.7 Weeks
Standard Deviation 0.0
|
19.4 Weeks
Standard Deviation 21.1
|
—
|
—
|
|
Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 2
Duration of disease control(N=14; N=6)
|
21.8 Weeks
Standard Deviation 6.1
|
21.5 Weeks
Standard Deviation 12.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatmentPopulation: patients treated in stage 2
Best RECIST Assessment as confirmed duration of disease control as per the independent central review (ICR) assessment according to the RECIST 1.0 criteria.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=36 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=32 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Best RECIST Assessment as Confirmed Duration of Disease Control as Per ICR for Stage 2
|
17.4 Weeks
Standard Deviation 5.0
|
18.4 Weeks
Standard Deviation 10.0
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomisation to disease progression in Stage 1 or death whichever occurred first before crossover.Population: Randomised set (RS).
PFS is defined as time from randomisation to until the occurrence of tumor progression or death, whichever occurred first, during Stage 1 of the trial. Median is calculated from the Kaplan-Meier curve for each treatment group.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Progression Free Survival (PFS) Before Crossover Based on Investigator Assessment
|
15.86 weeks
Interval 10.29 to 17.14
|
15.14 weeks
Interval 8.29 to 19.29
|
—
|
—
|
SECONDARY outcome
Timeframe: From first administration of study medication after cross over to disease progression in Stage 2 or death whichever came first after crossover.Population: Patients treated in stage 2
PFS is defined as time from first administration study medication after cross over until the occurrence of tumor progression or death, whichever came first, during Stage 2 of the trial. Median is calculated from the Kaplan-Meier curve for each treatment group.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=36 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=32 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Progression Free Survival (PFS) After Crossover Based on Investigator Assessment
|
7.93 weeks
Interval 4.29 to 14.43
|
6.43 weeks
Interval 4.14 to 8.29
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomisation to data cut-off date.Population: Randomised set (RS).
OS is defined as time from randomisation to death. Median is calculated from the Kaplan-Meier curve for each treatment group.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Overall Survival (OS)
|
35.86 Weeks
Interval 25.71 to 45.0
|
47.14 Weeks
Interval 24.14 to 64.71
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomisation to deterioration in HRQoL scores before crossover.Population: Randomised Set (RS)
Health related Quality of Life (HRQoL) for Time to deterioration was assessed using the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Head and Neck Cancer Module (H\&N35). Time to deterioration in HRQoL (defined as a 10-point change towards worsening from the baseline score on a 0-100 point scale) was determined for: * global health status (Questions 29 and 30 in EORTC QLQ C30) * pain (Questions 9 and 19 in EORTC QLQ C30) * swallowing (Questions 35 to 38 in EORTC QLQ-H\&N35)
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=62 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=62 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Time to Deterioration in HRQoL - Stage 1
pain (N=34; N=33)
|
2.73 months
Interval 1.48 to 5.88
|
4.63 months
Interval 2.92 to 8.61
|
—
|
—
|
|
Time to Deterioration in HRQoL - Stage 1
global health status (N=37; N=38)
|
2.83 months
Interval 1.91 to 5.85
|
3.94 months
Interval 2.96 to 7.39
|
—
|
—
|
|
Time to Deterioration in HRQoL - Stage 1
swallowing (N=33; N=34)
|
5.59 months
Interval 2.07 to 7.36
|
6.60 months
Interval 2.92 to 8.48
|
—
|
—
|
SECONDARY outcome
Timeframe: First administration of trial medication until 28 days after last drug administrationPopulation: Treated Set in Stage 1 : This analysis set included the randomized patients who took at least 1 dose of the randomized treatment (61 afatinib and 60 cetuximab patients. Treated set in Stage 2: This analysis set included all patients who received treatment: 36 patients in the afatinib and 32 patients in the cetuximab arm.
Patients with adverse events (AEs) resulting in Diarrhea, Skin Rash, dose reduction, treatment discontinuation and decreased cardiac left ventricular function Note: To asses the Decreased Cardiac left ventricular function, Left ventricular ejection fraction (LVEF) was assessed in patients treated with afatinib in Stage 1 and Stage 2 . And no patients in either group had a significant change in LVEF during Stage 1 or Stage 2 of the trial.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=61 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=60 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
n=36 Participants
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
n=32 Participants
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function
With AE leading to Diarrhea
|
49 number of participants
|
15 number of participants
|
22 number of participants
|
2 number of participants
|
|
Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function
With AE leading to skin rash
|
48 number of participants
|
46 number of participants
|
23 number of participants
|
14 number of participants
|
|
Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function
With AE leading to dose reduction
|
18 number of participants
|
2 number of participants
|
11 number of participants
|
0 number of participants
|
|
Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function
With AE leading to treatment discontinuation
|
23 number of participants
|
11 number of participants
|
8 number of participants
|
6 number of participants
|
SECONDARY outcome
Timeframe: First administration of trial medication until 28 days after last drug administrationPopulation: Treated Set in Stage 1 : This analysis set included the randomized patients who took at least 1 dose of the randomized treatment (61 afatinib and 60 cetuximab patients. Treated set in Stage 2: This analysis set included all patients who received treatment: 36 patients in the afatinib and 32 patients in the cetuximab arm.
Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=61 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=60 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
n=36 Participants
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
n=32 Participants
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE grade 1
|
3.3 percentage of participants
|
5.0 percentage of participants
|
5.6 percentage of participants
|
9.4 percentage of participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE grade 2
|
24.6 percentage of participants
|
41.7 percentage of participants
|
25.0 percentage of participants
|
37.5 percentage of participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE grade 3
|
39.3 percentage of participants
|
28.3 percentage of participants
|
25.0 percentage of participants
|
25.0 percentage of participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE grade 5
|
24.6 percentage of participants
|
16.7 percentage of participants
|
30.6 percentage of participants
|
15.6 percentage of participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE grade 4
|
8.2 percentage of participants
|
6.7 percentage of participants
|
13.9 percentage of participants
|
9.4 percentage of participants
|
SECONDARY outcome
Timeframe: Day 15Population: Pharmacokinetic Set (PK): The PK analysis was based on all patients who were treated with afatinib and who had evaluable plasma concentration data, which consisted of data for 60 patients in Stage 1 and 35 patients in Stage 2.
Cpre,ss,15 represents the pre-dose concentration of afatinib in plasma at steady state on day 15. Note: At day 15, values for afatinib 40 mg no values reported in stage 1 and stage 2.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=45 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=26 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 15 (Cpre,ss,15)
|
39.3 ng/mL
Geometric Coefficient of Variation 70.1
|
46.6 ng/mL
Geometric Coefficient of Variation 81.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 29Population: Pharmacokinetic Set (PK)
Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29. Note: At day 29, values for afatinib 40 mg no values reported in stage 2.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=9 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=33 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
n=22 Participants
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 29 (Cpre,ss,29)
|
8.84 ng/mL
Geometric Coefficient of Variation 206
|
31.7 ng/mL
Geometric Coefficient of Variation 97.7
|
45.9 ng/mL
Geometric Coefficient of Variation 48.9
|
—
|
SECONDARY outcome
Timeframe: Day 57Population: Pharmacokinetic Set (PK)
Cpre,ss,57 represents the pre-dose concentration of afatinib in plasma at steady state on day 57.
Outcome measures
| Measure |
Afatinib 50 mg - Stage 1
n=7 Participants
Patients were randomised to receive Afatinib 50 mg once daily (q.d.) in Stage 1.
|
Cetuximab 250 mg/m2 - Stage 1
n=16 Participants
Patients were randomized to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1.
|
Afatinib 50 mg - Stage 2
n=10 Participants
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
|
Cetuximab mg/m2 - Stage 2
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 57 (Cpre,ss, 57)
|
32.7 ng/mL
Geometric Coefficient of Variation 25.3
|
19.9 ng/mL
Geometric Coefficient of Variation 94.4
|
46.5 ng/mL
Geometric Coefficient of Variation 67.2
|
—
|
Adverse Events
Cetuximab 250 mg/m2 / Afatinib 50 mg - Stage 1
Serious events: 26 serious events
Other events: 59 other events
Deaths: 0 deaths
Afatinib 50 mg / Cetuximab 250mg/m2 - Stage 2
Serious events: 18 serious events
Other events: 34 other events
Deaths: 0 deaths
Cetuximab 250 mg/m2 / Afatinib 50 mg - Stage 2
Serious events: 13 serious events
Other events: 29 other events
Deaths: 0 deaths
Afatinib 50 mg / Cetuximab 250mg/m2 - Stage 1
Serious events: 36 serious events
Other events: 61 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cetuximab 250 mg/m2 / Afatinib 50 mg - Stage 1
n=60 participants at risk
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2.
|
Afatinib 50 mg / Cetuximab 250mg/m2 - Stage 2
n=36 participants at risk
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
Cetuximab 250 mg/m2 / Afatinib 50 mg - Stage 2
n=32 participants at risk
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2.
|
Afatinib 50 mg / Cetuximab 250mg/m2 - Stage 1
n=61 participants at risk
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Endocrine disorders
Hypercalcaemia of malignancy
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Eye disorders
Periorbital oedema
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
13.1%
8/61 • 1493 days
|
|
Infections and infestations
Respiratory tract infection
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Blood and lymphatic system disorders
Anaemia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Cardiac disorders
Cardiac arrest
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Cardiac disorders
Cardiopulmonary failure
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Cardiac disorders
Endocarditis noninfective
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Cardiac disorders
Myocardial infarction
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Cardiac disorders
Pericardial effusion
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Cardiac disorders
Pericarditis
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Gastrointestinal disorders
Dysphagia
|
1.7%
1/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Gastrointestinal disorders
Nausea
|
3.3%
2/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
2/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
General disorders
Asthenia
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
General disorders
Chest pain
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
General disorders
Chills
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
General disorders
Face oedema
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
General disorders
General physical health deterioration
|
5.0%
3/60 • 1493 days
|
16.7%
6/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
General disorders
Mucosal inflammation
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
General disorders
Oedema peripheral
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
General disorders
Pain
|
0.00%
0/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
General disorders
Pyrexia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Immune system disorders
Hypersensitivity
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Abscess limb
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Bacteraemia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Bronchitis
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Cellulitis
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Device related infection
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Device related sepsis
|
3.3%
2/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Endocarditis
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Infectious pleural effusion
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Lung infection
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Meningitis staphylococcal
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Pneumonia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
8.2%
5/61 • 1493 days
|
|
Infections and infestations
Sepsis
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Septic shock
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Infections and infestations
Toxic shock syndrome
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Injury, poisoning and procedural complications
Overdose
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Investigations
Weight decreased
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.7%
1/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Metabolism and nutrition disorders
Dehydration
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
13.1%
8/61 • 1493 days
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
3.3%
2/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Soft tissue necrosis
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Linitis plastica
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm malignant stage unspecified
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour compression
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
1.7%
1/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Nervous system disorders
Cerebrovascular accident
|
3.3%
2/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Nervous system disorders
Convulsion
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Nervous system disorders
Neuralgia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Nervous system disorders
Somnolence
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Nervous system disorders
Vocal cord paralysis
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Psychiatric disorders
Alcohol abuse
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Psychiatric disorders
Anxiety
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Psychiatric disorders
Disorientation
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Psychiatric disorders
Hallucination, auditory
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Renal and urinary disorders
Renal tubular necrosis
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.0%
3/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
1.7%
1/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Surgical and medical procedures
Gastrointestinal tube insertion
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Vascular disorders
Hypotension
|
0.00%
0/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
Other adverse events
| Measure |
Cetuximab 250 mg/m2 / Afatinib 50 mg - Stage 1
n=60 participants at risk
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2.
|
Afatinib 50 mg / Cetuximab 250mg/m2 - Stage 2
n=36 participants at risk
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
Cetuximab 250 mg/m2 / Afatinib 50 mg - Stage 2
n=32 participants at risk
Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2.
|
Afatinib 50 mg / Cetuximab 250mg/m2 - Stage 1
n=61 participants at risk
Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
16.7%
10/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
14.8%
9/61 • 1493 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Eye disorders
Conjunctivitis
|
11.7%
7/60 • 1493 days
|
11.1%
4/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Gastrointestinal disorders
Abdominal pain
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Gastrointestinal disorders
Cheilitis
|
3.3%
2/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Gastrointestinal disorders
Constipation
|
28.3%
17/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
18.8%
6/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
15/60 • 1493 days
|
58.3%
21/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
73.8%
45/61 • 1493 days
|
|
Gastrointestinal disorders
Dry mouth
|
8.3%
5/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
5/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Gastrointestinal disorders
Dysphagia
|
13.3%
8/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
Gastrointestinal disorders
Nausea
|
28.3%
17/60 • 1493 days
|
22.2%
8/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
36.1%
22/61 • 1493 days
|
|
Gastrointestinal disorders
Oral pain
|
3.3%
2/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Gastrointestinal disorders
Stomatitis
|
6.7%
4/60 • 1493 days
|
11.1%
4/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
8.2%
5/61 • 1493 days
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
12/60 • 1493 days
|
19.4%
7/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
24.6%
15/61 • 1493 days
|
|
General disorders
Asthenia
|
15.0%
9/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
12.5%
4/32 • 1493 days
|
16.4%
10/61 • 1493 days
|
|
General disorders
Fatigue
|
31.7%
19/60 • 1493 days
|
13.9%
5/36 • 1493 days
|
18.8%
6/32 • 1493 days
|
29.5%
18/61 • 1493 days
|
|
General disorders
Mucosal inflammation
|
18.3%
11/60 • 1493 days
|
19.4%
7/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
23.0%
14/61 • 1493 days
|
|
General disorders
Pyrexia
|
18.3%
11/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Infections and infestations
Nasopharyngitis
|
3.3%
2/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Infections and infestations
Paronychia
|
6.7%
4/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Infections and infestations
Upper respiratory tract infectio
|
1.7%
1/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Investigations
Weight decreased
|
13.3%
8/60 • 1493 days
|
13.9%
5/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
14.8%
9/61 • 1493 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
18.3%
11/60 • 1493 days
|
19.4%
7/36 • 1493 days
|
18.8%
6/32 • 1493 days
|
19.7%
12/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.0%
6/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
3.3%
2/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
5/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.3%
5/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
4/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
1.7%
1/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Nervous system disorders
Dysgeusia
|
1.7%
1/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Nervous system disorders
Dizziness
|
11.7%
7/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
8.2%
5/61 • 1493 days
|
|
Nervous system disorders
Headache
|
8.3%
5/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
15.6%
5/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Nervous system disorders
Paraesthesia
|
1.7%
1/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Psychiatric disorders
Anxiety
|
1.7%
1/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Psychiatric disorders
Confusional state
|
5.0%
3/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Psychiatric disorders
Insomnia
|
8.3%
5/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
12/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
3.3%
2/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.0%
9/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
8.2%
5/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
5/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
14.8%
9/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
3.3%
2/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
9.8%
6/61 • 1493 days
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
13.3%
8/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
12.5%
4/32 • 1493 days
|
13.1%
8/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
5.0%
3/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
0.00%
0/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
13.3%
8/60 • 1493 days
|
8.3%
3/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
19.7%
12/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
26.7%
16/60 • 1493 days
|
11.1%
4/36 • 1493 days
|
9.4%
3/32 • 1493 days
|
14.8%
9/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.3%
2/60 • 1493 days
|
5.6%
2/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
3.3%
2/60 • 1493 days
|
13.9%
5/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
5/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
0.00%
0/32 • 1493 days
|
13.1%
8/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
41.7%
25/60 • 1493 days
|
27.8%
10/36 • 1493 days
|
18.8%
6/32 • 1493 days
|
42.6%
26/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
18.3%
11/60 • 1493 days
|
2.8%
1/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
4.9%
3/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Skin toxicity
|
5.0%
3/60 • 1493 days
|
11.1%
4/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
3.3%
2/61 • 1493 days
|
|
Skin and subcutaneous tissue disorders
Xeroderma
|
5.0%
3/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
6.6%
4/61 • 1493 days
|
|
Vascular disorders
Hypertension
|
1.7%
1/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
6.2%
2/32 • 1493 days
|
1.6%
1/61 • 1493 days
|
|
Vascular disorders
Hypotension
|
3.3%
2/60 • 1493 days
|
0.00%
0/36 • 1493 days
|
3.1%
1/32 • 1493 days
|
8.2%
5/61 • 1493 days
|
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 Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication
- Publication restrictions are in place
Restriction type: OTHER