Journal of Oncology Translational Research

ISSN: 2476-2261

Open Access

Choosing the Best EGFR TKI in the Era of Precision Medicine


Zachary L Farmer, Kathryn F Mileham and Edward S Kim

The treatment of metastatic Non-small Cell Lung Cancer (mNSCLC) has evolved from traditional doublet chemotherapy to a model for precision medicine. Over the past fifteen years, the discovery of Epidermal Growth Factor Receptor (EGFR) mutations as key players in the pathogenesis of mNSCLC has transformed the care of patients with mNSCLC. EGFR Tyrosine Kinase Inhibitors (TKIs) have prolonged both progression free survival and overall survival in patients who harbor EGFR mutations. Most recently, the third generation EGFR TKI osimertinib has shown superior progression free survival compared to earlier TKIs. Osimertinib has also shown excellent penetration into the CNS, less CNS tumor progression, and even leptomeningeal disease response. The efficacy of EGFR TKIs in the CNS may allow clinicians to avoid or defer radiation therapy for CNS disease in select mNSCLC patients with EGFR mutations. The advent of circulating tumor DNA (ctDNA) has shown excellent diagnostic concordance with tumor biopsy in detecting EGFR mutations. While not the most sensitive tests, ctDNA is highly specific in uncovering EGFR mutations. In the future, ctDNA will likely avoid many unnecessary tissue biopsies in suspected lung cancer. As a marker of disease burden, ctDNA load will also play a key complementary role in determining response to therapy, disease resistance, and associated prognosis in EGFR mutated mNSCLC. In light of these remarkable advances, testing for mutations in EGFR, in addition to mutations in ALK, ROS-1, BRAF and PD-L1, is now more than ever the standard of care for mNSCLC, and critical to precision medicine.


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