Lung Cancer - EA5182

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)

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. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

Criteria 

• Patient must have advanced disease, defined as one of the following (per AJCC/IASLC 8th Edition):
  Stage IV disease or Stage IIIB disease not amenable to definitive multi-modality therapy or
  Recurrence after a prior diagnosis of stage I-III disease.
• Patient must have somatic activating sensitizing mutation in EGFR including (but not limited to):
  Exon 19 deletion; L858R; E709X; G719X; exon 19 insertions; L861Q; S768I
• Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible.
  (Test results from a CLIA-certified or similarly accredited laboratory are acceptable; no specific assay is mandated)
  (Plasma, cytology, or tumor tissue can be utilized for mutation testing)
• Patient must not have received any prior treatment with an EGFR TKI or with an anti-VEGF agent.
• Patient must not have had any prior systemic treatment for metastatic disease.
• Patient must not have any risk factors for anti-VEGF administration, specifically, hemoptysis, active
  cardiovascular disease, uncontrolled hypertension, significant proteinuria (screening urinalysis>300 mg/dl) and tumor invading major blood vessels.
• Patients who have received prior radiation therapy are eligible.
  Limited field stereotactic radiation or conventional radiation must have been completed ≥ 1 week prior to C1D1.
  More extensive field radiation (i.e., WBRT) must have been completed ≥ 2 weeks prior to study drug initiation.

Location(s): Hartford Hospital, Hospital of Central Connecticut and MidState Medical Center
Contact(s): Hayley Dunnick 860-972-5518