Stereotactic Radiosurgery or Other Local Ablation Then Erlotinib in Epidermal Growth Factor Receptor (EGFR)

Primary Objectives

- To estimate progression free survival (PFS) after locally ablative therapy and erlotinib in
EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy

Secondary Objectives

- To evaluate local control of sites previously progressive on erlotinib following
stereotactic radiosurgery (SRS) followed by erlotinib

- To estimate overall survival (OS) after locally ablative therapy and erlotinib in
EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy

- To characterize the toxicity of SRS

- To characterize the toxicity of erlotinib when preceded by SRS

Exploratory Objectives

- To explore if VeriStrat results at initial progression are associated with longer PFS or
OS after study treatment

- To explore if VeriStrat results following completion of SRS are associated with longer
PFS or OS after re-initiation of erlotinib

- To explore whether "poor" VeriStrat signatures ever turn to "good" signatures with the
study therapy, and to explore PFS and OS of patients whose signature changes

Inclusion Criteria:

- Written informed consent

- 18 years of age or older

- Histologically or cytologically confirmed stge IV EGFR-mutant NSCLC

- History of previous response to EGFR-TKI defined by a RECIST 1.1 criteria

- Progressive disease following EGFR-TKI therapy

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Adequate organ and marrow function

- Negative urine or serum pregnancy test for female patients

- Patients who can have children must agree to adequate contraception

Exclusion Criteria:

- Unresolved chronic toxicities greater than 2, measured by CTCAE v4

- Treatment with any FDA approved or experimental cancer treatment following progression
on EGFR-TKI

- Any history of previous greater than grade 3 toxicity attributable to erlotinib

- Pregnant or lactating female

- Any previous radiation to sites of planned Stereostatic Radiosurgery

- History of another malignancy

- Concomitant anticancer therapy, immunotherapy, or radiation therapy (within 4 weeks)

- Evidence of severe or uncontrolled systemic diseases

- Known hypersensitivity reaction or idiosyncrasy to erlotinib

- Psychological, familial, sociological, or geographical conditions

- Any other condition in investigator's opinion jeopardize compliance with protocol