Abstract
Background
Systemic treatment with tyrosine-kinase inhibitors (TKI) is the standard of care for advanced non-small cell lung cancer (NSCLC) patients who harbor EGFR mutations. Over 90% of patients have two most frequent mutations: deletion of exon 19 and exon 21 L858R substitution. In such patients, first line treatment with TKI is strongly recommended and produces a high response rate. It is less clear how patients harboring other, rare mutations will response to TKI, and experiences are still sparse. We analyzed the response to gefitinib, applied in first line treatment for advanced Serbian lung adenocarcinoma patients, in the last three years.
Methods
Chemonaïve patients with lung adenocarcinoma and stage IIIB and IV who were in performance status 0 or 1 were analyzed by real-time polymerase chain reaction (PCR) with regard to epidermal growth factor receptor (EGFR) mutations. Overall, 1,148 consecutive patients were included in the analysis, from June 2011 till April 2014. The group comprised of 697 males (60.7%) and 451 females (39.3%) of Caucasian descent. Patient age range was 20-85 years (median 61 years). Statistical analyses included testing of sample distribution for normality, parameters description and testing the differences between the parameters, with statistical significance set as P<0.05.
Results
A total of 121 (10.5%) mutated samples were found of which 69.4% in females (P=0.00018), giving the typical EGFR positivity picture of NSCLC patients in Caucasian population: 10-15% of aimed population. Apart from del19 (68 samples) and L858R (39 samples), 14 samples (1.2% of total) with rare mutations were found: L861Q (two samples), G719X (six samples), Ins (four samples) and two double mutants L861Q/G719X and G719X/S768I. Of these 14 patients, eight received gefitinib in first-line treatment. Response to treatment was as followed: two patients with SD and six with PD.
Conclusions
Rare mutations (1% in Serbian experience) were associated with poor response to gefitinib in EGFR mutated advanced adenocarcinoma patients. Small absolute number of patients does not allow further conclusions, but an ongoing study including more patients will hopefully show a clearer situation on this subject.
Keywords: Non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations, gefitinib