Trial Outcomes & Findings for An Open Label Trial of Afatinib (Giotrif) in Treatment-naive (1st Line) or Chemotherapy Pre-treated Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring EGFR Mutation(s) (NCT NCT01853826)

Last Updated: 2025-04-11

Results Overview

Number of patients with any treatment emergent adverse event (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

481 participants

Primary outcome timeframe

From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days.

Results posted on

2025-04-11

Participant Flow

Open-label, multicentre, single-arm trial to evaluate the safety, tolerability and efficacy of afatinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation(s) who had never been treated with an EGFR tyrosine kinase inhibitor (TKI).

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

Participant milestones

Participant milestones
Measure	Afatinib Treated-patients Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
Overall Study STARTED	481
Overall Study Treated	479
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	481

Reasons for withdrawal

Reasons for withdrawal
Measure	Afatinib Treated-patients Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
Overall Study Patients who switched to commercial drug	11
Overall Study Patient refused to continue medication	21
Overall Study Lost to Follow-up	2
Overall Study Non-compliant with protocol	4
Overall Study Other adverse events (AE)	62
Overall Study Worsening or AE of underlying cancer disease	24
Overall Study Progressive disease	342
Overall Study Other than listed	13
Overall Study Not treated - not signed privacy informed consent	2

Baseline Characteristics

An Open Label Trial of Afatinib (Giotrif) in Treatment-naive (1st Line) or Chemotherapy Pre-treated Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring EGFR Mutation(s)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Afatinib Treated-patients n=479 Participants Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
Age, Continuous	64.2 Years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	314 Participants n=5 Participants
Sex: Female, Male Male	165 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	465 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: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days.

Population: Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.

Number of patients with any treatment emergent adverse event (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Outcome measures

Outcome measures
Measure	Afatinib Treated-patients n=479 Participants Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
Number of Patients With Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0	478 Participants

Adverse Events

Afatinib Treated-patients

Serious events: 210 serious events

Other events: 268 other events

Deaths: 127 deaths

Serious adverse events

Serious adverse events
Measure	Afatinib Treated-patients n=479 participants at risk Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
Blood and lymphatic system disorders Coagulopathy	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Blood and lymphatic system disorders Thrombocytopenia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Acute coronary syndrome	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Acute myocardial infarction	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Atrial fibrillation	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Cardiac arrest	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Cardiac failure	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Cardiac failure acute	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Cardiac failure congestive	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Cardiac tamponade	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Cardiopulmonary failure	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Left ventricular dilatation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Myocardial infarction	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Pericardial effusion	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Cardiac disorders Ventricular hypokinesia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Eye disorders Glaucoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Abdominal pain	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Diarrhoea	3.3% 16/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Duodenal ulcer	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Dysphagia	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Gastric perforation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Gastritis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Gastritis erosive	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Intestinal infarction	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Intestinal obstruction	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Nausea	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Odynophagia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Oesophageal obstruction	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Pancreatitis acute	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Rectal haemorrhage	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Retroperitoneal haematoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Stomatitis	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Vomiting	1.5% 7/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Asthenia	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Chest pain	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Condition aggravated	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Death	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Disease progression	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Fatigue	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders General physical health deterioration	2.3% 11/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Hyperpyrexia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Mucosal inflammation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Multiple organ dysfunction syndrome	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Pain	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Pyrexia	0.84% 4/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Hepatobiliary disorders Cholecystitis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Hepatobiliary disorders Cholecystitis chronic	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Abscess	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Abscess neck	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Bacteraemia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations COVID-19	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Cavernous sinus thrombosis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Cellulitis	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Clostridial infection	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Clostridium difficile colitis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Conjunctivitis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Ear infection bacterial	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Enterocolitis bacterial	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Gastroenteritis	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Influenza	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Mastoiditis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Oral herpes	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Paronychia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Pneumocystis jirovecii infection	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Pneumonia	1.9% 9/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Pneumonia cytomegaloviral	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Pyelonephritis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Respiratory tract infection	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Sepsis	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Septic shock	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Urinary tract infection	1.0% 5/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Viral infection	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Accidental poisoning	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Concussion	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Craniofacial fracture	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Fall	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Femur fracture	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Hip fracture	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Limb injury	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Patella fracture	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Peripheral nerve injury	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Radius fracture	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Road traffic accident	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Toxicity to various agents	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Injury, poisoning and procedural complications Wound	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Alanine aminotransferase increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Aspartate aminotransferase increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Blood bilirubin increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Blood creatine phosphokinase increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Blood creatinine increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations C-reactive protein increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Hepatic enzyme increased	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Investigations Weight decreased	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Decreased appetite	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Dehydration	1.3% 6/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Electrolyte imbalance	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Hypokalaemia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Hyponatraemia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Iron deficiency	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Musculoskeletal and connective tissue disorders Back pain	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Musculoskeletal and connective tissue disorders Muscular weakness	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Musculoskeletal and connective tissue disorders Pathological fracture	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chromophobe renal cell carcinoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial sarcoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	7.5% 36/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma benign	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	2.3% 11/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to pancreas	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian granulosa cell tumour	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Aphasia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Cerebral haemorrhage	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Cerebral infarction	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Cerebrovascular accident	1.0% 5/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Cerebrovascular disorder	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Cognitive disorder	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Dementia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Dizziness	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Embolic stroke	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Epilepsy	0.84% 4/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Generalised tonic-clonic seizure	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Headache	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Hemiparesis	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Ischaemic stroke	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Memory impairment	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Myelopathy	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Neurological decompensation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Neuropathy peripheral	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Seizure	0.84% 4/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Somnolence	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Spinal cord compression	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Nervous system disorders Transient ischaemic attack	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Product Issues Device dislocation	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Psychiatric disorders Behaviour disorder	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Psychiatric disorders Bradyphrenia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Psychiatric disorders Confusional state	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Psychiatric disorders Hallucination	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Renal and urinary disorders Acute kidney injury	0.84% 4/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Renal and urinary disorders Hydronephrosis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Renal and urinary disorders Renal failure	1.7% 8/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Renal and urinary disorders Urinary retention	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Reproductive system and breast disorders Cervical dysplasia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Reproductive system and breast disorders Cystocele	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Reproductive system and breast disorders Uterine prolapse	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 11/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 16/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.63% 3/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.7% 13/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.3% 6/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Rash	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Surgical and medical procedures Surgery	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Deep vein thrombosis	0.84% 4/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Haematoma	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Peripheral ischaemia	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Peripheral vascular disorder	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Superior vena cava syndrome	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Thrombophlebitis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Vena cava thrombosis	0.21% 1/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Vascular disorders Venous thrombosis	0.42% 2/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.

Other adverse events

Other adverse events
Measure	Afatinib Treated-patients n=479 participants at risk Patients diagnosed with EGFR mutation positive non-small cell lung cancer (NSCLC) locally advanced or metastatic who have never been treated with EGFR tyrosine kinase inhibitors (TKI) received a daily dose of 40 milligrams (mg) of afatinib (Giotrif®), in the form of film-coated tablet over a 28 day cycle. Afatinib was taken orally with 250 milliliters (mL) of water at the same time of the day and without eating anything for at least 3 hours. Patients continued on treatment for as long as there was no disease progression or no other trial withdrawal criteria. The dose was reduced to 30 mg or 20 mg once daily when the initial dose was not tolerated by the patient.
Skin and subcutaneous tissue disorders Rash	29.9% 143/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Rash papular	5.6% 27/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Skin fissures	5.6% 27/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Diarrhoea	49.7% 238/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Nausea	6.7% 32/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Gastrointestinal disorders Stomatitis	8.8% 42/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Asthenia	10.9% 52/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Fatigue	7.3% 35/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Mucosal inflammation	11.3% 54/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
General disorders Pyrexia	6.3% 30/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Conjunctivitis	8.6% 41/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Infections and infestations Paronychia	17.7% 85/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Metabolism and nutrition disorders Decreased appetite	5.6% 27/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Cough	7.5% 36/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.3% 30/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Dermatitis acneiform	5.8% 28/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Dry skin	10.2% 49/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.
Skin and subcutaneous tissue disorders Pruritus	6.1% 29/479 • All-cause mortality, serious adverse events and other AEs: From first drug administration to last drug administration plus 28 days of residual effect period. Up to 3866 days. Treated set (TS): all patients who were dispensed afatinib and are documented to have taken at least one dose of afatinib.

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