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.