Randomized Phase III Study of Combination AZD9291 (Osimertinib) and Bevacizumab Versus AZD9291 (Osimertinib) Alone as First-Line Treatment for Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)
Objective
This phase III trial compares the effect of bevacizumab and AZD9291 (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.
Study Arms
- Active Comparator: Arm A (osimertinib)
- Experimental: Arm B (osimertinib, bevacizumab)
Eligibility
- Patient must have a pathologically confirmed diagnosis of non-squamous, non-small cell lung cancer (NSCLC)
- Patient must have advanced disease, defined as - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria
- Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, G709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Test results originating from a Clinical Laboratory Improvement Act (CLIA)-certified or similarly accredited laboratory are acceptable; no specific assay is mandated. If there is any question as to whether an EGFR mutation is sensitizing, please contact the primary study team
- Patients that have received prior radiation therapy are eligible. Radiation (whole-brain radiotherapy [WBRT] or stereotactic radiation) must have been completed at least two weeks prior to study registration
- Patient must have measurable disease. Baseline measurements of sites of disease must be obtained within 4 weeks prior to study registration. If a potential target lesion is previously irradiated without subsequent growth and/or is radiated after the imaging from which baseline measurements are obtained, they cannot be included as target lesions, and additional target lesions are required to meet criteria for measurable disease
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
- A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for 2 weeks prior to the start of treatment, while on study treatment, and for
- 6 weeks after the last dose of protocol treatment for female patients on the AZD9291 (osimertinib) alone arm
- 4 months after the last dose of protocol treatment for male patients on AZD9291 (osimertinib) alone arm
- 6 months after the last dose of protocol treatment for all patients on AZD9291 (osimertinib) plus bevacizumab combination arm
- NOTE: Female patients should also not breastfeed while on treatment and for 6 months after the last dose bevacizumab
- Leukocytes >= 3,000/mcL (obtained =< 14 days prior to registration)
- Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to registration)
- Platelets >= 100,000/mcL (obtained =< 14 days prior to registration)
- Hemoglobin >= 9 g/dL (obtained =< 14 days prior to registration)
- Total bilirubin and creatinine =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 14 days prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 14 days prior to registration)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if neurologically stable without glucocorticoid therapy after the stated washout period from radiation therapy (RT) or surgery provided the metastatic lesions are non-hemorrhagic
- Patients with untreated brain metastases or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required provided the metastatic lesions are non-hemorrhagic and are neurologically stable without glucocorticoid therapy
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
- Patient must have the ability to understand and the willingness to sign a written informed consent document and comply with study requirements
