ABSTRACT
BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins) represent approximately 10% of EGFR-mutant lung adenocarcinomas, and are associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Clinical outcomes in comparison with patients with sensitizing EGFR mutations are not well established. METHODS: Patients with stage IV lung adenocarcinomas with EGFR exon20ins were identified through routine molecular testing. Clinicopathologic data were collected. Overall survival (OS) was measured from the diagnosis of stage IV disease, and in patients treated with EGFR TKIs, the time to progression (TTP) on erlotinib was measured. RESULTS: One thousand eight hundred and eighty-two patients with stage IV lung adenocarcinomas were identified: 46 patients had EGFR exon20ins (2%), and 258 patients had an EGFR exon 19 deletion (exon19del)/L858R point mutation (14%). Among 11 patients with lung adenocarcinomas with EGFR exon20ins who received erlotinib, 3 patients (27%) had a partial response (FQEA, 1; ASV, 1; and unknown variant, 1). TTP for patients with EGFR exon20ins and patients with EGFR exon19del/L858R on erlotinib were 3 and 12 months, respectively (P < .01). Responses to chemotherapy were similar for patients with lung adenocarcinomas with EGFR exon20ins and patients with lung adenocarcinomas with EGFR exon19del/L858R. Median OS from the diagnosis of stage IV disease for patients with EGFR exon20ins and patients with EGFR exon19del/L858R was 26 months (95% confidence interval, 19 months-not reached n = 46) and 31 months (95% confidence interval, 28-33 months; n = 258), respectively (P = .53). CONCLUSIONS: The majority of patients with advanced lung adenocarcinomas harboring EGFR exon20ins do not respond to EGFR TKI therapy. Standard chemotherapy should be used as first-line therapy. These patients have an OS similar to that of patients with sensitizing EGFR mutations. Individuals with certain variants such as FQEA and ASV may respond to erlotinib.
Subject(s)
Adenocarcinoma/genetics , Drug Resistance, Neoplasm/genetics , Genes, erbB-1/genetics , Lung Neoplasms/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma of Lung , Aged , Antineoplastic Agents/therapeutic use , Erlotinib Hydrochloride/therapeutic use , Exons , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Mutagenesis, Insertional , Protein Kinase Inhibitors/therapeutic use , Treatment OutcomeSubject(s)
Certification , Licensure, Nursing , Occupational Health Nursing/standards , Canada , HumansABSTRACT
The structural gene for purine-nucleoside phosphorylase (NP) has been assigned to a subregion of chromosome 14 by somatic cell hybridization of male and female cells containing the balanced translocation t(X;14) (p22;q21). Peripheral lymphocytes were fused to a pseudodiploid HPRT-deficient established Chinese hamster cell line. 23 primary hybrid clones (10 derived from male and 13 from female cells) were isolated and maintained in HAT selective medium. Parallel subcultures from generations 16, 24, and 40 after clonal isolation were fully karyotyped and analyzed electrophorectically for expression of the human types of NP, HPRT, G6PD, and PGK. The human NP phenotype segregated discordantly with each human chromosome except chromosome 14 and the der(14),t(X;14) translocation chromosome. In all, 8 hybrids which had retained the der(X), t(X;14) translocation chromosome under HAT selective pressure and expressed human HPRT had lost the human NP phenotype. These results indicate localization of the NP gene in region 14pter leads to 14q21.
