Decision of Sponsor

Multicentre randomised (1:1) trial assessing the efficacy of whole brain radiotherapy in addition to Gefitinib for the management of brain metastasis in lung cancer patients with a mutated EGFR.

Lung cancer patients with newly diagnosed CNS metastasis with- at least one brain lesion measuring > 1 cm in longest dimension - not eligible for surgery or stereotactic radio-surgeryOpen-label, multicentre, national, randomised (1:1) phase II trialArm A: WBRT and Concurrent Gefitinib followed by Gefitinib Maintenance Arm B: Gefitinib

Inclusion Criteria:

• Patients must have signed a written informed consent form prior to any study specific screening procedures
• 18 years or older
• KPS ≥ 50%
• Histologically confirmed adenocarcinoma of the lung
• Activating mutation of EGFR
• Newly diagnosed CNS metastasis or in progression with at least one measurable lesion in the brain (defined as any lesion > 1 cm on T1-weighted contrast enhanced MRI)
• Patients could enter the study regardless of previous treatment (included chemotherapy) for metastatic extracranial disease, except TKI.
• No steroids or stable or decreasing dose of steroids for at least 5 days before the MRI evaluation.
• Adequate hematologic, liver and renal functions: neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; Hb ≥ 9 g/Dl; Total bilirubin < 1.5 x ULN; AST or ALT < 2.5 x ULN (< 5 x ULN in patients with liver metastases); Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min

Exclusion Criteria:

• Prior treatment of brain metastases with WBRT or TKI
• Patient eligible for radiosurgery or surgical resection
• Contre indication at the radiotherapy
• Leptomeningeal disease
• Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in-situ carcinoma of the cervix) within the the 5 years before study entry
• Prior treatment with Gefitinib or other TKI
• Pregnant or breast feeding women
• Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception