P3.02b-002 Treatment Outcome Comparison between Exon 19 and 21 EGFR Mutations after Second-Line TKIs in Advanced NSCLC Patients: Topic: EGFR Biomarkers

Abstract

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 NSCLC patients with and without brain and/or bone metastases in different EGFR tumor genotypes receiving EGFR-TKIs as a second-line treatment. The treatment outcomes of 166 NSCLC patients harboring either the exon 19 deletion or the L858R point mutation of EGFR treated by second-line TKIs were retrospectively reviewed. 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 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)]. The median PFS and OS for NSCLC patients with bone metastasis were 4.8 months (95% Cl, 4.0-5.6 months) and 12.9 months (95% Cl, 8.7-17.1 months), respectively. No significant difference was observed for patients with bone metastasis for different mutations. EGFR genotype and ECOG PS were independent predictors of PFS for both NSCLC patients with and without brain metastasis. Never smoking (P=0.001), exon 19 deletion (P=0.03), EGOC PS (0-1) (P<0.001) and no brain metastasis (p=0.01) were correlated with longer OS for all NSCLC patients. For patients with brain metastasis, age at disease progression (p=0.009), genotype (p=0.02) and EGOC PS (p<0.001) were independent predictors of OS. For patients with bone metastasis, EGOC PS (p<0.001) was an independent predictor for both PFS and OS. Female (P=0.01), never smoking (P=0.005), number of bone metastases (P=0.03) and EGOC PS (0-1) (P=0.002) were related to a longer PFS. EGOC PS (0-1) (P<0.001) was associated with a longer OS. Rash, fatigue, and anorexia were the three most frequent side effects observed No significant side effects difference between exon 19 and 21 mutation groups were observed. NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutations are significant prognostic factors for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment.