Identification of Epidermal Growth Factor Receptor Tyrosine-Kinase Mutations in Non-small Cell Lung Cancer: Testing Platform Matters

Personalized medicine using targeted therapies has revolutionized the management of non-small cell lung cancer (NSCLC) in the past decade. The discovery that sensitizing epidermal growth factor receptor (EGFR) mutations are predictive for therapeutic benefit from EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib marked the beginning of a new era in lung cancer therapeutics. Indeed, EGFR mutation testing is category A recommendation at the time of diagnosis for patients presenting with advanced-stage NSCLC. In our case, the original report of EGFR mutation testing using pyro-sequencing from the initial biopsy was reported out as wild-type/no mutation seen in the hot spots. However, the tumor had a long duration of response to erlotinib but later developed resistance, hence there was a high index of suspicion. Consequently, it was decided to retest the tumor with more sensitive technology. Next generation sequencing identified exon 19 deletion - a sensitizing mutation. This explained the excellent response on initiating erlotinib, however, exon 21 mutation was also reported which confers resistance to TKI. The case shows that test sensitivity can have a great impact on treatment decisions and if there is a high index of suspicion, initial testing and, or retesting using newer more sensitive technology should be considered.