Osimertinib With Stereotactic Radiosurgery (SRS) in Brain Metastases From EGFR Positive NSCLC

Inclusion Criteria:

Confirmed pathology of EGFR mutation positive NSCLC with new brain metastases.
Ability to care for self and ability to walk 50% of waking hours (ECOG Performance Status of 0-2)
1-10 brain metastases with intra-cranial brain metastasis must measure 3cm or less in the greatest dimension.
Hemoglobin ≥9 g/dL, White Blood Count Absolute ≥3.0 x 10^9/L, Granulocyte count ≥1.5 x 10^9/L, and platelet count ≥100 x 10^9/L
Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
AST and/or ALT ≤ 2 ULN (≤ 5 x ULN when clearly attributable to liver metastases)
Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance > 60ml/min
For women of childbearing potential-Negative pregnancy test within one week prior to start of therapy.
For all sexually active male and female patients of reproductive potential, employ two methods of highly effective and acceptable forms of contraception throughout the study and for 120 days following the final dose of osimertinib.

Exclusion Criteria:

Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF).
Significant intratumoral or peritumoral hemorrhage
Brain metastases within 5 mm of the optic chiasm or optic nerve
Brainstem metastases
Gastrointestinal disorders with diarrhea as a major symptom
Clinically significant or uncontrolled cardiac disease (NYHA functional classification of 3 or 4)
Pre-existing interstitial lung disease or pneumonitis
Unable to undergo brain MRI
HIV or Hepatitis B or C
Prior treatments must be resolved to an asymptomatic state at time of enrollment
Medical conditions that could cause safety risks
Currently receiving investigational cancer therapy.
Mean QT interval corrected heart rate (QTc)≥470ms calculated from 3 EKGs
Left Ventricular Ejection Fraction (LVEF) ≤ 50%
Use of strong CYP3A inhibitors
Use of strong CYP3A4 inducers
Use of potent CYP2C8 inhibitors
Hypersensitivity to osimertinib or any of its ingredients
corneal ulceration
pregnant or breast-feeding