Epidermal growth factor receptor (EGFR) mutations in a series of non-small-cell lung cancer (NSCLC) patients and response rate to EGFR-specific tyrosine kinase inhibitors (TKIs)

Abstract

INTRODUCTION Epidermal growth factor receptor (EGFR) mutation related to tyrosine kinase inhibitors' (TKIs) responsiveness in non-small cell lung cancer (NSCLC) has become an important issue for therapeutic decision-making in NSCLC patients. MATERIAL AND METHODS Sixty-nine Caucasian NSCLC patients were screened for mutations in the tyrosine kinase (TK) domain of EGFR by direct sequencing from December 2005 to September 2010. RESULTS Activating mutations in the EGFR TK domain were found in 8 of 69 (11.6%) (7 deletions in exon 19 and one L858R mutation in exon 21). Seven of those mutations were found in adenocarcinoma and one mutation in bronchiolo-alveolar carcinoma; five of them in females (one smoker) and three of them in males (one smoker). All patients carrying activating mutations in the TK domain of EGFR were treated with TKIs. Ten patients not carrying an activating mutation in EGFR, who progressed after chemotherapy, were also treated with compassionate use of EGFR-specific TKIs (gefitinib or erlotinib). An objective response (partial response) was observed in all patients carrying an activating mutation in EGFR that received TKIs. Median overall survival for these patients has not been reached, however mean survival has been estimated at 39.5 months (95% CI, 22-57). CONCLUSIONS As previously reported, EGFR TK mutational analysis was a predictive test for response to targeted therapy with EGFR TKIs. The early identification of these patients consistently attains disease response and clearly improves outcomes.

Clinicopathological and immunohistochemical profile of non-small cell lung carcinoma in a tertiary care medical centre in South India

“…The EGFR overexpression accounts for about 43-83% of NSCLC, being more common in squamous cell carcinoma (70%), followed by adenocarcinoma (50%) and, to a lesser extent, in large cell carcinoma. [31819] The EGFR mutation status is best determined by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) and protein expression determined by IHC with mutation-specific antibodies. EGFR is expressed in 50% of NSCLC, and its expression is correlated with poor prognosis.…”

EGFR Mutation Status and First-Line Treatment in Patients with Stage III/IV Non–Small Cell Lung Cancer in Germany: An Observational Study

“…Routine clinical practice management and outcomes data in Caucasian patients with EGFR mutation-positive NSCLC are limited to small, retrospective studies (18,19). The Registry for the Epidemiological and Scientific evaluation of EGFR mutation status in patients with newly diagnosed locally advanced or metastatic NSCLC (REASON) was a noninterventional study (NIS) initiated to address this need for evidence of the epidemiology of EGFR mutation-positive NSCLC and pharmacoeconomic data on EGFR mutation-positive NSCLC.…”

Detection and characterization of classical and “uncommon” exon 19 Epidermal Growth Factor Receptor mutations in lung cancer by pyrosequencing

“…Furthermore, a slightly higher amount of mutated cases compared to the literature data in the Western population [23] was observed, and this could be attributed to the high sensitivity of pyrosequencing. Such results were confirmed either with ARMS assay, that demonstrated a good concordance though providing information only in terms of presence/absence of classical mutations (with no information about any other alteration), and with Sanger sequencing that provides the exact nucleotide sequence (though with a lower sensitivity [10]).…”