Non-Small Cell Lung Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular Classification of NSCLC
These mutations are mutually exclusive, except for those in PIK3CA and EGFR mutations and ALK translocations.
EGFR and ALK mutations predominate in adenocarcinomas that develop in nonsmokers, and KRAS and BRAF mutations are more common in smokers or former smokers. EGFR mutations strongly predict the improved response rate and progression-free survival of EGFR inhibitors. In a set of 2,142 lung adenocarcinoma specimens from patients treated at Memorial Sloan Kettering Cancer Center, EGFR exon 19 deletions and L858R were found in 15% of tumors from former smokers (181 of 1,218; 95% CI, 13-17), 6% from current smokers (20 of 344; 95% CI, 4-9), and 52% from never-smokers (302 of 580; 95% CI, 48-56; P < .001 for ever- vs. never-smokers).
Fusions of ALK with EML4 genes form translocation products that occur in ranges from 3% to 7% in unselected NSCLC and are responsive to pharmacological inhibition of ALK by agents such as crizotinib. Other mutations that occur in less than 5% of NSCLC tumors include:
- HER2, present in 2% of tumors.
- PI3KCA, present in 2% of tumors.
- AKT1, present in 1% of tumors.
- BRAF mutations, present in 1% to 3% of tumors.
BRAF mutations are mutually exclusive of EGFR and KRAS mutations. Somatic mutations in MAP2K1 (also known as MEK) have been identified in 1% of NSCLC. MET oncogene encodes hepatocyte growth factor receptor. Amplification of this gene has been associated with secondary resistance to EGFR tyrosine kinase inhibitors.
Travis WD, Colby TV, Corrin B, et al.: Histological typing of lung and pleural tumours. 3rd ed. Berlin: Springer-Verlag, 1999.
Pao W, Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol 12 (2): 175-80, 2011.
Tiseo M, Gelsomino F, Boggiani D, et al.: EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant patient with both concomitant mutations. Lung Cancer 71 (2): 241-3, 2011.
D'Angelo SP, Pietanza MC, Johnson ML, et al.: Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol 29 (15): 2066-70, 2011.