Osimertinib and Bevacizumab in Treating Patients with Metastatic EGFR-Mutant Non-small Cell Lung Cancer

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 tyrosine kinase inhibitor (TKI)
• No prior treatment with a vascular endothelial growth factor (VEGF) inhibitor
• Measurable (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) indicator lesion not previously irradiated
• Karnofsky performance status (KPS) >= 70%
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• Total bilirubin =< 1.5 x ULN
• Creatinine =< 1.5 x ULN OR calculated creatinine clearance >= 60 ml/min
• Absolute neutrophil count (ANC) >= 1000 cells/mm^3
• Hemoglobin >= 8.0 g/dL
• Platelets >= 100,000/mm^3

Exclusion Criteria

• Any contra-indications to bevacizumab which include but are not limited to recent * Any previous venous thromboembolism > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 * Severe uncontrolled hypertension (systolic blood pressure >= 150 mmHg and/or diastolic blood pressure >= 100 mmHg) * 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 arrhythmia 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 hour [hr] urine > 2 gm/24 hr) * 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 (> 325 mg daily), clopidogrel (> 75 mg 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 gastrointestinal tract (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