• 18 years and older

• Provision of informed consent prior to any study specific procedures

• Histologically or cytologically confirmed NSCLC(non small cell lung cancer) , performed on a biopsy

• Documented activating EGFR mutation (Exon 19 deletion or L858R)

• Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required)

• Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease

• Documentation that the patient is a candidate for surgical resection of their lung cancer by certified surgeon

• Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1

⁃ All toxicity from previous chemotherapy, radiation therapy, or surgical procedures according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 recovered to Grade 1 .

⁃ Patients may receive supplements to meet this requirement this requirement

∙ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)

‣ Bilirubin =\< 1.5 x ULN (Patients with documented Gilbert's syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels)

‣ Leukocytes \> 3,000/mcL

‣ Hemoglobin \>= 9 g/dL, with no blood transfusions in the 28 days prior to study entry

‣ Absolute neutrophil count \> 1,500/mcL

‣ Platelets \> 100,000/mcL

‣ Creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \> 50 mL/min/1.73 m2 for patients with creatinine levels =\< 1.5 x upper limit above institutional normal

⁃ Ability to swallow oral medications

⁃ Women of childbearing potential (WoCBP) must have a negative serum pregnancy test and agree to use highly effective contraception, during the study and for 2 months following the last dose of osimertinib

⁃ Women NOT of childbearing potential: women who are permanently or surgically sterilized or postmenopausal

∙ Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion; tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude possibility of pregnancy; (the term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts)

‣ Women who have undergone tubal occlusion should be managed on trials as if they are of WoCBP (e.g. undergo pregnancy testing etc., as required by the study protocol)

⁃ Women will be considered postmenopausal if they are amenorrhoeic for 12 months without an alternative medical cause; the following age-specific requirements apply:

∙ Women under 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range

‣ Women over 50 years of age will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments

⁃ Acceptable contraception methods are:

∙ Total sexual abstinence (abstinence must be for the total duration of the trial and the follow-up period)

‣ Vasectomized sexual partner plus male condom (with participant assurance that partner received post-vasectomy confirmation of azoospermia)

‣ Tubal occlusion plus male condom

‣ Intra-uterine device - provided coils are copper-banded, plus male condom

‣ Intra-uterine system (IUS) levonorgestrel IUS (e.g., Mirena), plus male condom

‣ Medroxyprogesterone injections (Depo-Provera) plus male condom

‣ Etonogestrel implants (e.g., Implanon, Norplant) plus male condom

‣ Normal and low dose combined oral contraceptive pills, plus male condom

‣ Norelgestromin / ethinylestradiol transdermal system plus male condom

‣ Intravaginal device (e.g., ethinylestradiol and etonogestrel) plus male condom

‣ Cerazette (desogestrel) plus male condom (Cerazette is currently the only highly efficacious progesterone based pill) For more information, see Appendix E (Definitions of Women of Fertility and Acceptable Contraception Methods).

⁃ The following methods are considered not to be highly effective and are therefore not acceptable contraceptive methods: - Triphasic combined oral contraceptives; All progesterone only pills except, Cerazette; All barrier methods, if intended to be used alone; Non-copper containing intra-uterine devices; Fertility awareness methods; Coitus interruptus

⁃ Men must agree to the use of high-efficiency contraception.