First-Line EGFR-1 Tyrosine Kinase Inhibition in Patients With NSCLC With Mutant EGFR Gene

Inclusion Criteria:

* Histological or cytological diagnosis of inoperable, locally advanced, recurrent or metastatic (Stage IIIB or Stage IV) adenocarcinoma of the lung in a patient with a smoking history of \< 15 years and quit smoking \> 1 year before diagnosis.
* Evidence of disease but measurable disease is not mandatory.
* 18 years of age or older.
* ECOG performance status of 0 - 3.
* Patients not eligible for standard curative-intent treatment with surgery or chemo-radiotherapy.
* Life expectancy ³ 3 months.
* Prior therapy for NSCLC allowed for primary disease: surgery and radiotherapy and adjuvant or proto-adjuvant chemotherapy completed \> 6 months before inclusion
* Adequate bone marrow, hepatic and renal function:

Granulocyte count \> 1.5 x 109/L and platelet count \> 100 x 109/L Serum bilirubin must be \< 1.5 upper limit of normal (ULN). If alkaline phosphatase is \> 2.5 x ULN, SGOT (AST) and SGPT (ALT) must be \< 1.5 x ULN.

Serum creatinine \< 1.5 ULN or creatinine clearance \> 60 ml/min.

* Ability for giving informed consent for participating in the study and filling out FACT-L quality of life scales.
* Able to comply with study and follow-up procedures.
* Availability of tumour biopsy sample (fixed in formalin and, if possible, also snap frozen tumour sample). If frozen samples are available, these will be collected by central data management.
* Signed Informed Consent for performing mutation analysis and subsequent biomarker analysis.
* Separate signed Informed Consent for participation in the treatment phase of the study.
* Ability to take oral medication.
* For all females of childbearing potential a negative pregnancy test must be obtained within 48 hours before starting therapy.

Exclusion Criteria:

* Patients for whom urgent chemotherapy or radiotherapy is deemed necessary (e.g. rapidly progressive disease).
* Current symptomatic central nervous disorder, brain or leptomeningeal metastasis.
* Pre-existing symptomatic interstitial lung disease, not related to the current malignancy.
* Patients with a history of other malignancies, except patients with basal cell carcinoma of the skin or in situ carcinoma of the cervix with a disease free interval of ³ 5 years. Patients with a prior history of other good prognosis malignancies more than 5 years since end of treatment and in un-maintained complete remission also can be considered for inclusion
* Prior therapy with systemic anti-tumour therapy with HER1/EGFR inhibitors (small molecule or monoclonal antibody) or chemotherapy
* Significant malabsorption syndrome or disease affecting the gastrointestinal tract function
* Pregnant or breast-feeding women; for women in reproductive condition, a negative pregnancy test is required.
* Concomitant food or drug intake which potentially impairs absorption and metabolisation of RTKI's.
* Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
* Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease).
* Any significant ophthalmological abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions.