Background: Mutations in the epidermal growth factor receptor (EGFR) gene induce sensitivity to targeted therapy of lung adenocarcinoma with tyrosine kinase inhibitors, but not all patients respond equally to treatment. The aim of this study was to determine the influence of patient (gender, age at diagnosis, smoking and performance status) and tumor (EGFR mutation type, T, N, M, localization of metastases) characteristics on the outcome of gefitinib therapy.
Methods: A total of 400 consecutive chemonaive lung adenocarcinoma patients, stage IIIB or IV, performance status 0, 1 or 2 from various centers in Serbia were analyzed. The group consisted of 245 males (61%) and 155 females (39%) of Caucasian descent. Patient age range was 20-84 years, median 60 years. Detection of EGFR mutations was performed by real-time polymerase chain reaction (PCR). Patients harbouring EGFR mutations were treated with gefitinib in the first line until progression in two centers in Serbia. Statistical analysis was performed using Chi-square, Fisher’s exact, Wilcoxon’s and Log-Rank tests; P<0.05 was considered significant.
Results: EGFR mutations were detected in 54 patients (13.5%), 34 female (63%) and 20 male (37%) (χ2=15.42, P<0.001), 46 (30 female, 16 male) were treated with gefitinib. Of these patients, 26 had deletion in exon 19, 16 had L858R substitution, two had G719X, one had an insertion in exon 20 and one was a double mutant G719X/S768I. Follow-up period was 2-27 months (median 8 months). Overall survival (OS) median was not reached in the investigated time frame. Progression-free survival (PFS) rate was 37.5% after 1 year and 20% after 2 years, with a median of 8 months (95% CI: 6-16 months). Female patients had significantly longer PFS (median 15 vs. 4 months, P=0.01) and OS (median not reached vs. 19 months, P=0.04) than males. Other investigated patient and tumor characteristics did not show statistically significant influence on the outcome of gefitinib therapy.
Conclusions: Our results show that in the Serbian population the outcome of gefitinib therapy is mostly influenced by the female gender.
