Inclusion Criteria:

- Histologically or cytologically confirmed, unresectable locally advanced (stage IIIB
with pleural effusion) and/or metastatic (stage IV) NSCLC

- No previous therapy for advanced/metastatic NSCLC is allowed

- age >18 years

- bidimensionally measurable disease

- non-smokers (or ex-smokers with less than 5 pack-years smoking history)

- adenocarcinoma histology

- performance status (WHO) 0-3

- adequate liver (serum bilirubin <1.5 times the upper normal limit (UNL); AST and ALT
<2.5 times the UNL in the absence of demonstrable liver metastases, or <5 times the
UNL in the presence of liver metastases); adequate renal function (serum creatinine
<1.5 times the UNL); and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x
109 /L) function

- previous radiotherapy, either in the adjuvant setting or for the treatment of
metastatic disease is allowed provided that the measurable lesions are outside the
radiation fields

- patient able to take oral medication

- tissue sample for tumour mutational analysis is required

Exclusion Criteria:

- serious chronic skin conditions (e.g. psoriasis, eczema) that would preclude study
participation

- active infection

- history of significant cardiac disease (unstable angina, congestive heart failure,
myocardial infarction within the previous 6 months, ventricular arrhythmias)

- malnutrition (loss of ≥ 20% of the original body weight)

- performance status: 4

- psychiatric illness or social situation that would preclude study compliance

- pregnant or lactating women