Uncommon mutations in epidermal growth factor receptor and response to first and second generation tyrosine kinase inhibitors: A case series and literature review

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2018-01, Vol.115, p.135-142
• Main Authors: Galli, Giulia, Corrao, Giulia, Imbimbo, Martina, Proto, Claudia, Signorelli, Diego, Ganzinelli, Monica, Zilembo, Nicoletta, Vitali, Milena, de Braud, Filippo, Garassino, Marina Chiara, Lo Russo, Giuseppe
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biomarkers, Pharmacological - metabolism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; EGFR; ErbB Receptors - genetics; Ex-Smokers; Fatal Outcome; Female; Gene Duplication; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Mutation - genetics; Protein Kinase Inhibitors - therapeutic use; Response; Tyrosine kinase inhibitor; Uncommon mutation
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2017.12.002

•EGFR mutations are associated to efficacy of TKIs in NSCLC.•Data about prevalence and response to TKIs of rare EGFR alterations are scarce.•Literature review shows that a wide range of responses to TKIs may be observed.•A personalized approach based on available data must be warranted in these cases. Epidermal growth factor receptor (EGFR) is the most common driver gene involved in non small cell lung cancer (NSCLC) growth, being found in approximately 10–15% of Caucasian and 40% of Asian patients. A wide variety of pathogenic mutations, deletions, insertions and duplications have been described in EGFR exons 18–21. The presence of the most common among them (e.g. exon 21 L851R and exon 19 deletions) is associated to response to first and second generation EGFR tyrosine kinase inhibitors (TKIs), which have demonstrated clear superiority over chemotherapy in terms of both progression free survival (PFS) and overall survival (OS) in all treatment lines. However, scarcity of data exists in literature about the response of rarer EGFR alterations to first and second generation TKIs, most works consisting in sporadic case reports and small case series. In this review we aim to discuss the available evidence about this topic, in order to derive suggestions for clinical practice. Furthermore, we report seven cases of patients with lung tumors harboring uncommon EGFR mutations, treated in our Institution with first or second generation TKIs.