Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages
IIA, IIB, and IIIA non-small cell lung cancer (NSCLC) after complete resection. Cisplatin and
pemetrexed combination is the standard regimen for lung adenocarcinoma in adjuvant setting.
The BR. 19 trial reported adjuvant gefitinib after complete resection of early stage
NSCLC(stage IB 49%, II 38%, III 13%) did not confer disease free survival(DFS) or overall
survival(OS) advantage in overall population. While the median gefitinib treatment time is
only 4.8 months. There are only 76 patients with EGFR mutations included in this analysis.
The study closed prematurely in 2005.
Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor
receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR
mutation rate was 30% in Chinese NSCLC. Patients harboring these mutations in their tumors
show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase
III trial is studying gefitinib and synchronous pemetrexed/cisplatin chenmotherapy to see how
well it works compared to pemetrexed/cisplatin chenmotherapy alone in treating patients who
have undergone surgery for stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR activating
mutation in Asian population.
Inclusion Criteria:
- Written informed consent provided.
- Males or females aged ≥18 years, < 70 years.
- Able to comply with the required protocol and follow-up procedures, and able to
receive oral medications.
- Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with
EGFR exon 19 deletions and exon 21 L858R activating mutation.
- Patient who can start the investigational therapy within 3-6 weeks after the complete
resection
- ECOG performance status 0-1.
- Life expectancy ≥12 weeks.
- Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and
Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or
exceed this level).
- Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN),
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in
subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
- Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
- Female subjects should not be pregnant or breast-feeding.
Exclusion Criteria:
- Known severe hypersensitivity to gefitinib or any of the excipients of this product.
- Known severe hypersensitivity to pre-medications required for treatment with cisplatin
/ vinorelbine doublet chemotherapy.
- Inability to comply with protocol or study procedures.
- A serious concomitant systemic disorder that, in the opinion of the investigator,
would compromise the patient's ability to complete the study.
- A serious cardiac condition, such as myocardial infarction within 6 months, angina, or
heart disease.
- Interstitial pneumonia.
- Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib,
gefitinib, cetuximab, trastuzumab).
- Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g.
monoclonal antibody therapy).
- Patients with prior radiotherapy
- History of another malignancy in the last 5 years with the exception of the
following:Other malignancies cured by surgery alone and having a continuous
disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin
and cured in situ carcinoma of the uterine cervix are permitted.
- Any unstable systemic disease (including active infection, uncontrolled hypertension,
unstable angina, congestive heart failure, myocardial infarction within the previous
year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic
disease).
- Eye inflammation or eye infection not fully treated or conditions predisposing the
subject to this.
- Evidence of any other disease, neurological or metabolic dysfunction, physical
examination or laboratory finding giving reasonable suspicion of a disease or
condition that contraindicated the use of an investigational drug or puts the subject
at high risk for treatment-related complications.
- Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
- Patients who harbouring exon 20 T790M mutation.
