Trial Outcomes & Findings for Afatinib Treatment for Patients With EGFR Mutation Positive NSCLC Who Are Age 70 or Older (NCT NCT02514174)

NCT ID: NCT02514174

Last Updated: 2020-03-30

Results Overview

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 25 participants
• Primary outcome timeframe: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
• Results posted on: 2020-03-30

Participant Flow

Open-label, non-randomized, Phase IV, single arm study

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Measure	Afatinib Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Overall Study STARTED	25
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	25

Reasons for withdrawal

Measure	Afatinib Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Overall Study Patient refused to continue medication	1
Overall Study Adverse Event	2
Overall Study Study closed by sponsor	9
Overall Study Progressive disease	11
Overall Study Treatment change	1
Overall Study Treated off study with Afatinib.	1

Baseline Characteristics

Afatinib Treatment for Patients With EGFR Mutation Positive NSCLC Who Are Age 70 or Older

Baseline characteristics by cohort

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Age, Continuous	79.2 years STANDARD_DEVIATION 5.4 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days

Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

Outcome measures

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Percentage of Participants Reporting an Adverse Event (AE) Leading to Dose Reduction of Afatinib	32.0 Percentage Interval 14.9 to 53.5

SECONDARY outcome

Timeframe: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days

Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.

Percentage of participants with adverse event being diarrhoea of CTCAE grade 3 or higher.

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

Outcome measures

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Percentage of Participants With Adverse Event = Diarrhoea of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Higher	8.0 Percentage of participants

SECONDARY outcome

Timeframe: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days

Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.

Percentage of participants with adverse event = rash/acne (grouped term) of CTCAE grade 3 or higher.

MedDRA preferred terms that described AEs of similar nature were grouped together as "grouped term" to ensure that important events would not be underestimated.

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

Outcome measures

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Percentage of Participants With Adverse Event = Rash/Acne (Grouped Term) of CTCAE Grade 3 or Higher	0.0 Percentage of participants

SECONDARY outcome

Timeframe: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days

Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.

Percentage of participants with adverse event = stomatitis (grouped term) of CTCAE grade 3 or higher.

MedDRA preferred terms that described AEs of similar nature were grouped together as "grouped term" to ensure that important events would not be underestimated.

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

Outcome measures

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Percentage of Participants With Adverse Event = Stomatitis (Grouped Term) of CTCAE Grade 3 or Higher	4.0 Percentage of participants

SECONDARY outcome

Timeframe: On-treatment period + 28 days (residual effect period), up to 1057 + 28 days

Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set.

Percentage of participants with adverse event = paronychia (grouped term) of CTCAE grade 3 or higher.

MedDRA preferred terms that described AEs of similar nature were grouped together as "grouped term" to ensure that important events would not be underestimated.

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

Outcome measures

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Percentage of Participants With Adverse Event = Paronychia (Grouped Term) of CTCAE Grade 3 or Higher	8.0 Percentage of participants

SECONDARY outcome

Timeframe: On-treatment period, up to 1057 days

Population: All participants who received at least one dose of afatinib were included in the treated set. The analyses of safety and efficacy were performed on the treated set. The 'Number Analyzed' is the 'Number at risk' at the respective time point, that is the number of participants being treated with afatinib 30 mg at the respective time point.

Time to first dose reduction of afatinib caused by adverse events is defined as time from the date of the first administration of afatinib to the date of first dose reduction of afatinib caused by adverse events. Participants without AEs leading to dose reduction were censored at date of last intake of afatinib.

On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent from study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).

The cumulative probability of no dose reduction at the respective time point is given by the Kaplan-Meier estimate at the respective time point based on time to first dose reduction of afatinib caused by adverse events.

Outcome measures

Measure	Afatinib n=25 Participants Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Time to First Dose Reduction of Afatinib Caused by Adverse Events 0 months (= First administration of afatinib)	1.0 Probability Interval 1.0 to 1.0
Time to First Dose Reduction of Afatinib Caused by Adverse Events 3 months	0.7889 Probability Interval 0.5642 to 0.9064
Time to First Dose Reduction of Afatinib Caused by Adverse Events 6 months	0.7450 Probability Interval 0.5176 to 0.8768
Time to First Dose Reduction of Afatinib Caused by Adverse Events 9 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 12 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 15 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 18 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 21 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 24 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 27 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 30 months	0.6519 Probability Interval 0.4214 to 0.8091
Time to First Dose Reduction of Afatinib Caused by Adverse Events 33 months	0.6519 Probability Interval 0.4214 to 0.8091

Adverse Events

Afatinib 30 mg

Serious events: 10 serious events

Other events: 25 other events

Deaths: 7 deaths

Serious adverse events

Measure	Afatinib 30 mg n=25 participants at risk Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Gastrointestinal disorders Diarrhoea	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Nausea	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Rectal haemorrhage	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Vomiting	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Pneumonia	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Urinary tract infection	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Injury, poisoning and procedural complications Fall	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Injury, poisoning and procedural complications Fracture displacement	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Injury, poisoning and procedural complications Humerus fracture	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Injury, poisoning and procedural complications Joint dislocation	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Dehydration	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Hyponatraemia	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Hypovolaemia	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Seizure	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Syncope	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Renal and urinary disorders Acute kidney injury	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Cough	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.0% 1/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.

Other adverse events

Measure	Afatinib 30 mg n=25 participants at risk Giotrif® / Gilotrif® (Afatinib) starting at 30 mg daily dose All participants received the same treatment (afatinib) with starting dose of 30 milligram (mg) per day with one possible dose reduction to 20 mg per day. Mode of administration: Orally one film-coated tablet, once daily
Blood and lymphatic system disorders Anaemia	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Eye disorders Dry eye	28.0% 7/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Eye disorders Vision blurred	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Abdominal pain	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Abdominal pain upper	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Constipation	24.0% 6/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Diarrhoea	88.0% 22/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Dry mouth	32.0% 8/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Dyspepsia	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Haemorrhoids	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Nausea	36.0% 9/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Oral pain	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Proctalgia	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Rectal haemorrhage	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Stomatitis	36.0% 9/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Gastrointestinal disorders Vomiting	24.0% 6/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Chills	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Fatigue	48.0% 12/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Gait disturbance	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Non-cardiac chest pain	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Oedema	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Oedema peripheral	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Pain	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
General disorders Pyrexia	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Bronchitis	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Conjunctivitis	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Fungal skin infection	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Nail infection	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Paronychia	24.0% 6/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Pneumonia	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Sinusitis	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Upper respiratory tract infection	32.0% 8/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Infections and infestations Urinary tract infection	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Injury, poisoning and procedural complications Contusion	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Injury, poisoning and procedural complications Skin abrasion	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Investigations Weight decreased	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Decreased appetite	32.0% 8/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Dehydration	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Hypokalaemia	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Hypomagnesaemia	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Metabolism and nutrition disorders Hyponatraemia	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Arthralgia	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Back pain	28.0% 7/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Flank pain	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Joint swelling	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Muscle spasms	20.0% 5/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Musculoskeletal and connective tissue disorders Pain in extremity	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Dizziness	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Headache	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Hypoaesthesia	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Neuropathy peripheral	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Nervous system disorders Paraesthesia	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Psychiatric disorders Anxiety	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Psychiatric disorders Insomnia	20.0% 5/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Cough	28.0% 7/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	24.0% 6/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	32.0% 8/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Nasal dryness	20.0% 5/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Productive cough	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Alopecia	20.0% 5/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Dermatitis acneiform	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Dry skin	52.0% 13/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Erythema	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Hair texture abnormal	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Nail discolouration	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Onychoclasis	28.0% 7/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Pruritus	16.0% 4/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Rash	64.0% 16/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	20.0% 5/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Scab	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Skin atrophy	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Skin discolouration	8.0% 2/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Skin exfoliation	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.
Skin and subcutaneous tissue disorders Skin fissures	12.0% 3/25 • On-treatment period+28 days, up to 1057+28 days. On-treatment period=First administration of afatinib until progression or intolerable AEs or other reasons necessitating withdrawal (participant withdrew consent or was diagnosed with interstitial lung disease or was no longer able to receive study treatments or had a significant deviation from the protocol or eligibility criteria). Time Frame for All-Cause Mortality is On-treatment period + Follow-Up, up to 1096 days. Adverse events (AEs) were reported for the treated set which comprises all participants who received at least one dose of afatinib. From 28 days after last trial drug intake new AEs were only reported if they were considered related to trial drug.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee The rights of the investigator and of the sponsor with regard to publication of the results of this trial were described in a separate agreement between the investigator or the trial site and the sponsor. As a general rule, no trial results were to be published prior to finalization of the clinical trial report.
• Publication restrictions are in place

Restriction type: OTHER