Abstract
IntroductionTreatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn't respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs.MethodsAmong the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses.ResultsOf 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48–63.26, P<0.0001; 9.4 vs. 17.3 months, HR = 2.74, 95% CI, 1.52–4.94, P = 0.0008; and 58% vs. 82% in 6, 37% vs. 60% in 12, and 19 vs. 40% at 24 months, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR = 47.22, 95% CI, 17.88–124.73, P<0.001 and HR = 2.74, 95% CI, 1.43–5.24, P = 0.002, respectively). However, none of the covariates except of the presence of EGFR exon 19 deletion in the tumors was significantly associated with better treatment efficacy.ConclusionsA subset of NSCLC EGFR-mutant patients displayed unfavorable survival despite EGFR TKI administration. This observation reinforces the urgent need for biomarkers effectively predicting the non-responders and for drug development overcoming primary resistance to EGFR TKIs. In addition, optimal therapeutic strategies to prolong the survival of non-responders need to be investigated.
Highlights
Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations
NSCLC-not otherwise specified (NOS) and 1 squamous cell carcinoma (SCC), patients who received EGFR TKIs as the front-line treatment for their advanced NSCLC with EGFR mutations were identified for the analyses (Figure 1), with a mean age: 68.2613.0 years, and median follow-up time: 9.8 months
We reconfirmed that a subset of NSCLC patients who were treated with EGFR TKIs did not experience marked tumor shrinkage despite the presence of EGFR mutations and clearly demonstrated that performance status (PS) and overall survival (OS) strikingly differed in non-responders and responders (1.8 vs. 10.3 months, P,0.0001 and 9.4 vs. 17.3 months, P = 0.0008, respectively)
Summary
Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. Epidermal growth factor receptor (EGFR) mutation status has been shown to be significantly associated with tumor response to EGFR tyrosine kinase inhibitors (TKIs)[1,2], leading to the routine assessment of the presence of EGFR mutations in advanced non-small cell lung cancers (NSCLC), adenocarcinomas[3,4]. 20–40% of NSCLC patients do not experience tumor reduction following EGFR TKI administration despite the presence of EGFR mutations in their tumors. This issue has not been well addressed. PFS in NSCLC EGFR-mutant patients whose tumors do not significantly shrink after targeted therapy is rarely reported, contributing to the lack of comprehensive information about the treatment outcome of this subset of NSCLC patients
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