Efficacy of Egfr Tyrosine Kinase Inhibitors (Egfr Tkis) in Patients with Egfr-Mutated Non-Small Cell Lung Cancer Except Both Exon 19 Deletion and Exon 21 L858R: a Retrospective Analysis in Korea

Abstract

ABSTRACT Aim: NSCLC can be defined by various molecular criteria, especially by the status of EGFR mutation. Two major EGFR mutations are exon 19 deletions (del-19) and L858R in exon 21 which account for 85%. But, other rare or complex EGFR mutations have not been fully described in terms of response to EGFR-TKI and other clinical outcomes. We performed this study to investigate the clinical significance and efficacy to EGFR TKIs in NSCLC patients with rare or complex EGFR mutations. Methods: We retrospectively reviewed data for consecutive patients with advanced NSCLC who were genotyped for EGFR mutation and treated with TKI. Subjects with EGFR wild type, del-19 alone, or L858R alone were excluded from this analysis. Rare mutation was defined as any mutation other than del-19 or L858R in exon 21 and complex mutation was defined as two or more different mutations co-existing within the same tumor sample. Results: Between January 2008 and December 2011, a total of 1,738 patients underwent EGFR genotyping. Among them, 88 (5.1%) had rare or complex mutations and 54 were treated with TKI. The median age was 58.0 years (range: 28–79 years), and 25 were males. Thirty patients were never-smokers and 48 had adenocarcinomas. Thirty-three patients had single rare mutations and 21 had complex mutations. The most frequent mutation was insertion in exon 20 (22.7%), followed by L858R (10.7%), duplication in exon 20 (9.3%), del-19 (8.0%), G719A (6.7%), G719S (5.3%), and S768I (5.3%). Response was evaluated in 50 patients. Partial response was achieved in 11 (20.4%) patients and stable disease in 20 (37.0%) patients. Disease control rate was 57.4%. The median PFS was 2.6 months (95% CI; 0.0-5.4 months) at a median follow-up duration of 381.0days (range; 10-1307 days). Forty-two patients had died at the time of the present evaluation. The median OS was 12.7 months (95% CI; 7.2-18.2 months). Conclusions: These results suggest that rare or complex EGFR mutation confer inferior response and survival than common mutations. Given the heterogeneity in clinical features and outcomes to EGFR TKIs, further efforts with large number of patients to sub-classify these patients will be needed. Disclosure: All authors have declared no conflicts of interest.