Trial Outcomes & Findings for Afatinib (BIBW 2992) QTcF Trial in Patients With Relapsed or Refractory Solid Tumours (NCT NCT00875433)

NCT ID: NCT00875433

Last Updated: 2013-12-30

Results Overview

OR is defined as complete response and partial response (PR) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST) for solid tumours (excluding glioblastomas).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 60 participants
• Primary outcome timeframe: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
• Results posted on: 2013-12-30

Participant Flow

Participant milestones

Measure	All Patients Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Overall Study STARTED	60
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	60

Reasons for withdrawal

Measure	All Patients Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Overall Study Progressive disease	41
Overall Study Other Adverse Event	14
Overall Study Withdrawal by Subject	2
Overall Study Other	3

Baseline Characteristics

Afatinib (BIBW 2992) QTcF Trial in Patients With Relapsed or Refractory Solid Tumours

Baseline characteristics by cohort

Measure	All Patients n=60 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Age, Continuous	58.7 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Population: Treated Set (TS). TS consisted of all patients who received at least one dose of trial medication.

OR is defined as complete response and partial response (PR) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST) for solid tumours (excluding glioblastomas).

Outcome measures

Measure	All Patients n=60 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Objective Response (OR)	1 Participants with OR

PRIMARY outcome

Timeframe: The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.

Population: All patients in TS who had at least 1 time-matched pair of QT measurements available from baseline and from Day 14 of treatment.

Average time-matched QT corrected by the Fridericia formula (QTcF) change from baseline to day 14 over 1 to 24 hours following administration of afatinib.

Outcome measures

Measure	All Patients n=49 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Average Time-matched QT Corrected by the Fridericia Formula (QTcF) Change From Baseline to Day 14	-0.3 ms Standard Error 1.5

SECONDARY outcome

Timeframe: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Population: All patients from TS who progressed or died.

PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas) as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.

Outcome measures

Measure	All Patients n=53 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Progression-free Survival (PFS)	10.6 weeks Interval 7.4 to 15.0

SECONDARY outcome

Timeframe: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Population: TS.

Overall survival (OS) is defined as time from start of treatment to death.

Outcome measures

Measure	All Patients n=53 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Overall Survival (OS)	39.6 weeks Interval 23.3 to

SECONDARY outcome

Timeframe: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Population: TS.

Disease control was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).

Outcome measures

Measure	All Patients n=60 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Disease Control	32 Participants

SECONDARY outcome

Timeframe: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Population: TS.

Duration of Disease control (DC). DC was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).

Outcome measures

Measure	All Patients n=32 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Duration of Disease Control (DC)	15.3 weeks Interval 15.0 to 24.0

SECONDARY outcome

Timeframe: Day 14

Population: All patients from TS with data for QTcF on day 14

Notable findings are defined as a QTcF>500 ms or an increase in QTcF of >60ms.

Outcome measures

Measure	All Patients n=51 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Patients With Notable Findings in QTcF on Day 14	1 Participants

SECONDARY outcome

Timeframe: Day 14

Population: All patients from TS with data for ECG on day 14

Patients with clinically relevant findings in Electrocardiogram data (ECG) on day 14.

Outcome measures

Measure	All Patients n=51 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Patients With Clinically Relevant Findings in ECG on Day 14	1 Participants

SECONDARY outcome

Timeframe: Baseline and day 14 (at 1, 2, 3, 4, 5, 6, 7, 10, 24 hours post-dose )

Population: All patients in TS who had at least 1 time-matched pair of QT measurements available from either Day1 or Day 14 of treatment.

Individual QTcF measurements at each time-point. Response was defined as the change from baseline. Analysis adjusted for baseline using a mixed model.

Outcome measures

Measure	All Patients n=49 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 1:00 h (N=48)	1.6 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 2:00 h (N=48)	1.2 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 3:00 h (N=49)	-2.1 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 4:00 h (N=49)	-2.5 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 5:00 h (N=49)	-2.3 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 6:00 h (N=49)	-0.4 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 7:00 h (N=48)	0.2 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 10:00 h (N=49)	0.2 ms Standard Error 2.2
Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point Time-point 24:00 h (N=48)	0.6 ms Standard Error 2.2

SECONDARY outcome

Timeframe: The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.

Population: All patients in TS who had at least 1 time-matched pair of QT measurements available from baseline and from Day 14 of treatment.

Average time-matched QT change from baseline to day 14 over 1 to 24 hours following administration of afatinib.

Outcome measures

Measure	All Patients n=49 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Average Time-matched QT Change From Baseline to Day 14	-0.4 ms Standard Error 2.6

SECONDARY outcome

Timeframe: Day 14

Population: All patients from TS with data for QTcF on day 14

Number of Patients with notable findings in QT on day 14. Notable findings are defined as a QT>500 ms.

Outcome measures

Measure	All Patients n=51 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Patients With Notable Findings in QT on Day 14	0 Participants

SECONDARY outcome

Timeframe: The day before the first drug dose (baseline) and the day 14.

Population: All patients in TS who had at least 1 time-matched pair of QT measurements available from baseline and from Day 14 of treatment.

Average time-matched heart rate change from baseline to day 14.

Outcome measures

Measure	All Patients n=49 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Average Time-matched Heart Rate Change From Baseline to Day 14.	0.1 bpm Standard Error 1.2

SECONDARY outcome

Timeframe: First administration of trial medication until 28 days after last administration of trial medication

Population: All patients from TS with adverse events

Highest Common Terminology Criteria (CTC) grade for adverse events

Outcome measures

Measure	All Patients n=60 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Highest CTC Grade for Adverse Events Grade 1	1 Participants
Highest CTC Grade for Adverse Events Grade 2	19 Participants
Highest CTC Grade for Adverse Events Grade 3	27 Participants
Highest CTC Grade for Adverse Events Grade 4	4 Participants
Highest CTC Grade for Adverse Events Grade 5	9 Participants

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1

Population: TS.

AUC0-24 represents the area under the concentration curve of afatinib in plasma from 0 to 24 hours on Day 1.

Outcome measures

Measure	All Patients n=56 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Area Under Curve 0-24 Hours (AUC0-24) on Day 1	482 ng*h/mL Geometric Coefficient of Variation 55.6

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1

Population: TS.

Cmax represents the maximum measured concentration of afatinib in plasma on Day 1.

Outcome measures

Measure	All Patients n=60 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Maximum Concentration (Cmax)	44.7 ng/mL Geometric Coefficient of Variation 58.9

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1

Population: TS.

tmax represents the time from dosing to the maximum concentration of afatinib in plasma on Day 1.

Outcome measures

Measure	All Patients n=60 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Time From Dosing to the Maximum Concentration (Tmax)	3.06 hours Interval 0.9 to 6.17

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14

Population: TS.

AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau (24h) at steady state (Day14).

Outcome measures

Measure	All Patients n=44 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)	1250 ng*h/mL Geometric Coefficient of Variation 53.3

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14

Population: TS.

Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state (Day 14).

Outcome measures

Measure	All Patients n=44 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)	86.6 ng/mL Geometric Coefficient of Variation 55.2

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14

Population: Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.

tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state (Day 14).

Outcome measures

Measure	All Patients n=44 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)	3.07 hours Interval 1.0 to 7.05

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14

Population: Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.

R_A,AUC represents the accumulation ratio of AUC values after multiple dose administration over a uniform dosing interval t between days 1 and 14

Outcome measures

Measure	All Patients n=42 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Accumulation Ratio of AUC Values (R_A,AUC)	2.67 ratio Geometric Coefficient of Variation 53.4

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14

Population: Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.

R_A,Cmax represents the accumulation ratio of Cmax values after multiple dose administration over a uniform dosing interval t between days 1 and 14

Outcome measures

Measure	All Patients n=44 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Accumulation Ratio of AUC Values (R_A,Cmax)	2.05 ratio Geometric Coefficient of Variation 58.5

SECONDARY outcome

Timeframe: 0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14

Population: Subset of TS, restricted to patients with adequate protocol compliance, i.e. patients without important protocol violations.

PTF represents the percentage peak trough fluctuation. PTF is defined as difference between maximum and minimum concentration at steady state divided by the average concentration multiplied with 100 to report as percentage.

Outcome measures

Measure	All Patients n=44 Participants Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Percentage Peak Trough Fluctuation (PTF)	97.6 percentage of peak trough fluctuation Geometric Coefficient of Variation 37.8

Adverse Events

All Patients

Serious events: 34 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Patients n=60 participants at risk Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Blood and lymphatic system disorders Anaemia	3.3% 2/60 • First administration of trial medication until 28 days after last administration of trial medication
Cardiac disorders Cardiac arrest	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Cardiac disorders Myocardial ischaemia	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Cardiac disorders Tachycardia	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Abdominal pain	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Abdominal pain lower	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Abdominal pain upper	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Diarrhea	11.7% 7/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Duodenal ulcer	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Dysphagia	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Nausea/Vomiting	10.0% 6/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Small intestinal obstruction	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Stomatitis	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Cellulitis	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Lower respiratory tract infection	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Lung infection	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Pneumonia	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Upper respiratory tract infection	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Urinary tract infection	3.3% 2/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Urosepsis	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Investigations Electrocardiogram QT prolonged	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Metabolism and nutrition disorders Decreased appetite	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Metabolism and nutrition disorders Dehydration	8.3% 5/60 • First administration of trial medication until 28 days after last administration of trial medication
Metabolism and nutrition disorders Hyponatraemia	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Metabolism and nutrition disorders Hypovolaemia	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal neoplasm	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer metastatic	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Nervous system disorders Convulsion	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Psychiatric disorders Confusional state	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Renal and urinary disorders Renal disorder	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Renal and urinary disorders Renal insufficency	8.3% 5/60 • First administration of trial medication until 28 days after last administration of trial medication
Renal and urinary disorders Urinary retention	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 2/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 2/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication
Skin and subcutaneous tissue disorders Rash/acne	3.3% 2/60 • First administration of trial medication until 28 days after last administration of trial medication
Renal and urinary disorders Ureteric obstruction	1.7% 1/60 • First administration of trial medication until 28 days after last administration of trial medication

Other adverse events

Measure	All Patients n=60 participants at risk Patients with tumours known to historically (over)express epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER) 2 with and without brain metastases, and patients with recurrent glioblastoma receiving an oral dose of Afatinib 50 mg once daily (qd)
Eye disorders Ocular effect	13.3% 8/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Abdominal pain	10.0% 6/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Abdominal pain upper	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Constipation	16.7% 10/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Diarrhea	73.3% 44/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Dyspepsia	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Dysphagia	8.3% 5/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Nausea/Vomiting	46.7% 28/60 • First administration of trial medication until 28 days after last administration of trial medication
Gastrointestinal disorders Stomatitis	45.0% 27/60 • First administration of trial medication until 28 days after last administration of trial medication
General disorders Oedema peripheral	8.3% 5/60 • First administration of trial medication until 28 days after last administration of trial medication
General disorders Pain	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
General disorders Pyrexia	11.7% 7/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Lower respiratory tract infection	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Nail effect	13.3% 8/60 • First administration of trial medication until 28 days after last administration of trial medication
Infections and infestations Urinary tract infection	8.3% 5/60 • First administration of trial medication until 28 days after last administration of trial medication
Metabolism and nutrition disorders Decreased appetite	38.3% 23/60 • First administration of trial medication until 28 days after last administration of trial medication
Metabolism and nutrition disorders Dehydration	10.0% 6/60 • First administration of trial medication until 28 days after last administration of trial medication
Musculoskeletal and connective tissue disorders Back pain	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Musculoskeletal and connective tissue disorders Muscle spasms	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Nervous system disorders Fatigue	51.7% 31/60 • First administration of trial medication until 28 days after last administration of trial medication
Nervous system disorders Headache	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Renal and urinary disorders Dysuria	8.3% 5/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Cough	13.3% 8/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 6/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Epistaxis	15.0% 9/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.7% 4/60 • First administration of trial medication until 28 days after last administration of trial medication
Skin and subcutaneous tissue disorders Dry skin	13.3% 8/60 • First administration of trial medication until 28 days after last administration of trial medication
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	11.7% 7/60 • First administration of trial medication until 28 days after last administration of trial medication
Skin and subcutaneous tissue disorders Rash/acne	75.0% 45/60 • First administration of trial medication until 28 days after last administration of trial medication

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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 of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER