Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs

Abstract

Introduction: Activating mutations in the epidermal growth factor receptor gene (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Long-term survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients and identify clinical factors associated with overall survival (OS).

Methods: Patients with EGFR-mutant metastatic lung adenocarcinoma who had been treated with erlotinib or gefitinib at Dana-Farber Cancer Institute between 2002 and 2009 were included. OS was analyzed.

Results: Among 137 patients, median progression-free survival and OS were 12.1 months (95% CI: 10.2-13.5) and 30.9 months (95% CI: 28.2-35.7), respectively. Twenty patients (14.6%) were 5-year survivors. In multivariate analysis, exon 19 deletions (hazard ratio [HR] = 0.63, 95% CI: 0.44-0.91, p = 0.01), absence of extrathoracic (HR = 0.62, 95% CI: 0.41-0.93, p = 0.02) or brain metastasis (HR = 0.48, 95% CI: 0.30-0.77, p = 0.002), and not a current smoker (HR = 0.23, 95% CI: 0.09-0.59, p = 0.002) were associated with prolonged OS. Age; sex; stage at diagnosis; liver, bone, or adrenal metastasis; specific TKI; and line of TKI therapy were not associated with OS.

Conclusions: Our data suggest that the rate of 5-year survival among patients with EGFR-mutant metastatic lung adenocarcinoma treated with erlotinib or gefitinib is 14.6%. Exon 19 deletions and absence of extrathoracic or brain metastasis are associated with prolonged survival. On the basis of our findings, clinicians can gain an enhanced estimation of long-term outcomes in this population.

Keywords: EGFR; Non–small cell lung cancer; TKI; long-term survival.

Figure 1

Kaplan-Meier plot of (A) progression-free survival and (B) overall survival for all patients in the study cohort. Median survivals are annotated in months.

Figure 2

Kaplan-Meier plots of overall survival according to the parameters of: the (A) exon of EGFR mutation (exon 19: n = 76; exon 21: n = 54; exon 18: n = 4), (B) presence of extrathoracic metastasis (yes: n = 79; no: n = 58), (C) presence of brain metastasis (yes: n = 30; no: n = 107), and (D) smoking status (never: n = 77; former: n = 55; current: n = 5). Median survival values are annotated in months. Hazard ratio (HR) according to the univariate analysis is as listed. For (A), HR is calculated for exon 19 vs either exon 18 or 21 EGFR mutation.