Efficacy and Safety Study of Afatinib to Treat Lung Cancer Patients

Inclusion Criteria: * Any stage not suitable for radical treatment * Either: Confirmed activating EGFR mutation (exons 18-21; e.g. L858R, exon 19 deletions, exon 20 insertions, T790M, list is not exhaustive), and WHO PS 0-3 Or No tissue suitable for EGFR genotyping, failed genotype, or EGFR genotyping unavailable, and NSCLC Adenocarcinoma sub-type, and Eligible smoking history: Never smoker (\<100 cigarettes in lifetime), or Former smoker (stopped \>1year ago and ≤10 pack-years) and WHO PS 0-2 * Unsuitable for or patient declining chemotherapy due to significant co-morbidity * Measurable disease according to RECIST version 1.1 * Adequate haematopoietic, hepatic and renal function defined as follows: Absolute neutrophil count (ANC) ≤1.5 x 109/L and platelet count ≤100 x 109/L * Bilirubin ≤1.5 x ULN, ALT (SGPT) ≤3 x ULN (or ≤ 5 x ULN in cases of liver metastases) * Serum creatinine clearance ≥45 ml/min * Palliative radiotherapy allowed unless to a solitary target lesion * Age 18 or over (no upper age limit) * Written informed consent that is consistent with ICH-GCP guidelines Exclusion Criteria: * Previous treatment with afatinib (BIBW 2992), or any EGFR-directed inhibitor * Any concurrent anticancer systemic therapy * Prior chemotherapy for relapsed and/or metastatic NSCLC * Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and registration * Suitable for radical radiotherapy * Palliative radiotherapy within 2 weeks prior to registration * Palliative radiotherapy to a solitary target lesion * Surgery (other than biopsy) within 4 weeks prior to registration * Inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption, any medical co- morbidity affecting gastrointestinal absorption * Patients with current or pre-existing interstitial lung disease * Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's participation in the trial * Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE version 4.0 Grade ≥3 diarrhoea of any etiology at baseline * Active brain metastases (defined as stable for \<4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants and/or leptomeningeal disease). Steroids will be allowed if administered as a stable (same) dose for at least one month before trial entry. * Any other current malignancy or malignancy diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer) * History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3 or more, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to registration * Symptomatic left ventricular failure with NYHA classification of 3 or more * Active viral hepatitis and/or known HIV positive * Known or suspected active drug or alcohol abuse * Use of any investigational drug within 8 weeks of registration. * Known allergy to BIBW 2992 or other ingredients. * Patients on steroids must have been on the same dose for at least 4 weeks. * Inability to understand or to comply with the requirements of the trial, trial protocol or to provide informed consent. * Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial * Women who are pregnant or breast feeding * Requirement for treatment with any of the prohibited concomitant medications listed in protocol