Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations

Abstract

Background: Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes.Methods: The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model.Results: The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the exon 19 L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. No significant difference on PFS and OS was observed between exon 19 deletion and L858R mutation group for patients with bone metastasis. EGFR genotype and ECOG PS were independent predictors of PFS. Never smoking, exon 19 deletion, EGOC PS (0-1) and no brain metastasis were correlated with longer OS. No significant difference on side effect between exon 19 and 21 mutation group was observed.Conclusions: NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutation is a significant prognostic factor for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment.

WITHDRAWN: EGFR exon 19 deletion is associated with favorable overall survival after first-line icotinib therapy in advanced non-small cell lung cancer patients: a retrospective, multiple-center, real-world study

“…A meta-analysis of 13 eligible trials involving 912 patients [21] showed that the two-year survival rate of the 19 deletion group was significantly higher than the 21 L858R group (OR 5.27, 95% CI 1.76-15.71; p = 0.003). There were similar results in a meta-analysis of icotinib [22,23]. Therefore, EGFR exon 19 deletion is associated with favorable OS after first-line gefitinib therapy in advanced non-small cell lung cancer patients.…”

The impact of EGFR mutations on the incidence and survival of stages I to III NSCLC patients with subsequent brain metastasis

“…Therefore, the different phosphotyrosine patterns between these two mutations may be associated with differential response durations of the EGFR TKIs. A recent study further showed that the exon 19 deletion group had a longer median PFS than the L858R mutation group (6.7 vs. 3.9 months, p<0.001) in patient with BM [ 65 ]. Some research showed that NSCLC patients with exon 19 deletion had more and smaller metastases with a reduced extent of peritumoral brain edema compared with patients with wild-type EGFR alleles.…”

Validation of the graded prognostic assessment for lung cancer with brain metastases using molecular markers (lung-molGPA)

“…The observed survival differences between the present study and the one reported by Sperduto et al [ 28 ] are in line with the hypothesis that continuous improvements of multimodal care translate into better outcome. With the advent of targeted drugs with high efficacy in molecularly-defined subgroups [ 10 , 11 , 31 ], and possibly also immunotherapy [ 32 ], further improvement can be expected.…”