Study Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer

Exclusion Criteria

• •1. EGFR T790M mutation alone or exon 20 insertions as unique mutation
• •2. Tumors with a squamous component
• •3. Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if \> 6 months before randomisation)
• •4. Radiotherapy to any site for any reason within 28 days prior to randomization (palliative radiotherapy to bone lesions is allowed if ≥ 14 days before randomization)
• •5. Full-dose anticoagulation with warfarin
• •6. Current or recent (within 10 days of enrolment) use of aspirin (\>325 mg/day) or chronic use of other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity
• •7. Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited =\< 7 days prior to registration
• •8. Receiving any medications or substances that are inducers of CYP3A4 use of inducers are prohibited =\< 7 days prior to registration
• •9. Inadequate coagulation parameters:
• •* activated partial thromboplastin time (APTT) \>1.5 x the upper limit of normal (ULN) or
• •* INR \>1.5
• •10. Inadequate liver function, defined as:
• •* serum (total) bilirubin \>1.5 x ULN
• •* AST/SGOT or ALT/SGPT \>2.5 x ULN
• •11. Inadequate renal function, defined as:
• •* serum creatinine \>2.0 mg/dl or \>177 micromol/l
• •* urine dipstick for proteinuria \>2+. Patients with \> o = 1+ proteinuria at baseline dipstick analysis must undergo a 24-hour urine collection and must demonstrate ≤1g of protein in their 24-hour urine collection.
• •12. Pregnancy or breast-feeding
• •13. Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \>100 mmHg on antihypertensive medications)
• •14. History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation
• •15. History of any of the following within 6 months prior to randomisation: serious systemic disease, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
• •16. Serious, non-healing wound, ulcer, or bone fracture
• •17. Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization
• •18. Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months
• •19. In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization
• •20. Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization
• •21. Anticipation of need for a major surgical procedure during the course of the study
• •22. Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption
• •23. Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or his/her ability to comply with study requirements
• •24. Any other invasive malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA)
• •25. Brain metastasis
• •26. Patients who have had radiotherapy ≥ 4 weeks prior to the first dose of study treatment, but who are still experiencing acute toxic effects of radiotherapy
• •27. Known HIV positive patients (patients with both acute or chronic infection are excluded)
• •28. Active HBV or HCV infection (patients with chronic non-active infection are eligible)
• •29. Any already known inflammatory changes of the surface of the eye at baseline
• •30. Any other concomitant pathologies or laboratory alterations that prevent or contraindicate the use of erlotinib or bevacizumab.