Personalized treatment of EGFR mutant and ALK-positive patients in NSCLC.
BACKGROUND
The epidermal growth factor receptor (EGFR) is mutated in 15% of adenocarcinomas of the lung. In addition, the anaplastic lymphoma kinase (ALK) is altered in 8% of adenocarcinomas of the lung. Treatment of EGFR mutant and ALK translocation-positive tumors in NSCLC with tyrosine kinase inhibitors (TKI) results in a dramatic therapeutic response and has revolutionized therapy. Unfortunately, resistance to TKIs invariably develops. Many promising new therapies are under investigation to overcome the resistance.


METHODS
We analyzed the current primary literature and recent national meetings to evaluate the clinical characteristics and therapeutic implications of relevant treatments for EGFR mutant and ALK-positive NSCLC in the first-line, acquired resistance, and adjuvant settings.


CONCLUSIONS
Treatment with EGFR TKIs in the first-line setting of EGFR mutant NSCLC results in a significant clinical benefit. Several promising third generation EGFR TKIs are being evaluated in Phase II and III trials in the acquired resistance setting. Crizotinib is superior to chemotherapy in the first-line setting for ALK-positive NSCLC. Ceritinib is effective and approved for ALK-positive NSCLC in the acquired resistance setting. Continued investigation is needed to develop novel therapies to overcome acquired resistance to TKIs.
Lung Cancer Program, University of Pittsburgh Cancer Institute , Pittsburgh, PA , USA.
Aswin
A
Somasundaram
Mark A
MA
Socinski
Timothy F
TF
Burns
D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
EGFR; NSCLC; acquired resistance; anaplastic lymphoma kinase