Are exon 19 deletions and L858R different in early stage lung adenocarcinoma?

Abstract

Introduction

Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the two mutational types in the early stage lung adenocarcinoma is unknown.

Methods

We enrolled consecutive patients with operable adenocarcinoma which harbored 19del or L858R to investigate the clinicopathologic characteristics and prognostic outcomes.

Results

Between 2008 and 2013, a total of 607 patients with 19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and disease-associated factors were well-balanced between 19del and L858R patients. Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the two groups. After relapse, 19del was associated with a better post-recurrence survival (PRS) than L858R (p = 0.016). Multivariate analysis demonstrated that mutational types (HR = 1.521, 95% CI: 1.106–2.093, p = 0.01) and tyrosine kinase inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301–0.592, p < 0.001) were independent predictors of PRS. The 19del and L858R patients were similar regarding recurrent patterns, except on pleural/chest wall metastasis (26.0% vs. 12.2%, p = 0.007).

Conclusions

Patients with the early stage lung adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After recurrence, both could benefit from TKI therapy without the need for a second biopsy, but 19del seemed to be associated with better PRS.

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