A Randomised, Open-label Phase IIb Trial of Afatinib Versus Gefitinib as First-line Treatment of Patients With EGFR Mutation Positive Advanced Adenocarcinoma of the Lung
1. Pathologically confirmed diagnosis of Stage IIIB / IV adenocarcinoma of the lung.
2. Documented activating epidermal growth factor receptor mutation (Del19 and/or L858R)
with tumour tissues.
3. At least one measurable lesion according to response evaluation criteria in solid
tumours version 1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
5. Age >= 18 years.
6. Adequate organ function as defined by the following criteria:
Serum aspartate transaminase(AST) and serum alanine transaminase(ALT) =< 3 x upper limit
of normal (ULN), or AST and ALT =<5 x ULN if liver function abnormalities are due to
underlying malignancy Total serum bilirubin =<1.5 x ULN Absolute neutrophil count (ANC)
>=1.5 x 109/L Creatinine clearance > 45ml / min Platelets >= 75 x 109/L
1. Prior systemic chemotherapy for stage IIIB or IV non-small cell lung cancer.
Neo-/adjuvant chemotherapy, chemoradiation or radiotherapy is permitted if at least
12 months has elapsed prior to disease progression.
2. Prior treatment with epidermal growth factor receptor targeting small molecules or
3. Major surgery within 4 weeks of study randomisation.
4. Active brain metastases
5. Meningeal carcinomatosis.
6. Previous or concomitant malignancies at other sites, except effectively treated
non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ
or effectively treated malignancy that has been in remission for more than 3 years
and is considered to be cured in the opinion of investigator.
7. Known pre-existing interstitial lung disease.
8. Clinically relevant cardiovascular abnormalities as judged by the investigator.
9. Cardiac left ventricular function with resting ejection fraction of less than
institutional lower limit of normal.
10. Women of child-bearing potential (WOCBP) and men who are able to father a child,
unwilling to be abstinent or use adequate contraception prior to study entry, for the
duration of study participation and for at least 2 months after treatment has ended.
11. Pregnancy or breast-feeding.
12. Active hepatitis and/or known HIV carrier
13. Any prohibited concomitant medications for therapy with afatinib or gefitinib