Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

Inclusion criteria

• Written informed consent
• Advanced biopsy-proven metastatic non-small cell lung cancer
• Somatic activating mutation in EGFR
• No prior treatment with an EGFR TKI
• No prior treatment with a VEGF inhibitor
• Measurable (RECIST 1.1) indicator lesion not previously irradiated
• Karnofsky performance status (KPS) ≥ 70%
• Age >18 years old
• Adequate organ function

• AST, ALT ≤ 3 x ULN
• Total bilirubin ≤ 1.5x ULN
• Creatinine ≤ 1.5x ULN OR calculated creatinine clearance > 60ml/min
• Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
• Hemoglobin≥8.0 g/dL
• Platelets ≥100,000/mm3

Exclusion criteria

• Any contra-indications to bevacizumab which include but are not limited to recent

• Any previous venous thromboembolism > NCI CTCAE Grade 3
• Severe uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥ 100mmHg)
• Cardiovascular disease including stroke of myocardial infarction <6 months prior to study enrollment, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrythmia uncontrolled by medication
• Hemorrhagic brain metastases. Asymptomatic (not requiring escalating doses of steroids) brain metastases are acceptable.
• History of severe proteinuria (urine dipstick ≥ 2+ or 24 hr urine > 2gm/24hr)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• History of a central nervous system disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
• Significant vascular disease (e.g. aortic aneurysm requiring surgical repair)≥ 6 months prior to study enrollment
• History of hemoptysis (≥1/2 teaspoon of bright red blood per episode) within the last 3 months
• Evidence of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Current or recent (within 10 days of study drug start) use of aspirin (>325mg daily), clopidogrel (>75mg daily).
• Recent initiation of full dose oral or parental anticoagulants that have not been in place for at least 2 weeks.
• Tumor invading or abutting major blood vessels
• Tumor histology classified by squamous cell histology.
• Any history of abdominal fistula or GI perforation within 6 months of study enrollment
• Pregnant or lactating women
• Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol
• Any radiotherapy within 1 week of starting treatment on protocol
• Any major surgery within 4 weeks of starting treatment on protocol
• Any evidence of clinically significant interstitial lung disease
• Known hypersensitivity to any component of bevacizumab and osimertinib