This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

PRIMARY OBJECTIVE: I. To evaluate progression-free survival (PFS) of osimertinib (AZD9291) and bevacizumab versus osimertinib (AZD9291) alone as first-line treatment for patients with metastatic EGFR-mutant lung cancers. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS). II. To evaluate best objective response rate and duration of objective response. III. To evaluate time to central nervous system (CNS) progression and CNS PFS. IV. To evaluate toxicity of the combination regimen. CORRELATIVE OBJECTIVES: I. To characterize mechanisms of resistance to osimertinib (AZD9291) and osimertinib (AZD9291) with bevacizumab first-line therapy through post-progression circulating tumor-derived deoxyribonucleic acid (ctDNA). II. To assess for ctDNA clearance on study treatment and associate ctDNA clearance with clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive osimertinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive osimertinib PO QD on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO), multigated acquisition scan (MUGA), computed tomography (CT) and may undergo magnetic resonance imaging (MRI) and blood and urine sample collection on study. After completion of study treatment, patients are followed up every 3 months for 10 years.