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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.

SUBMITTER: Lin JJ

PROVIDER: S-EPMC4979601 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Lin Jessica J JJ Cardarella Stephanie S Lydon Christine A CA Dahlberg Suzanne E SE Jackman David M DM Jänne Pasi A PA Johnson Bruce E BE

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20151225 4

<h4>Introduction</h4>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).<h4>Methods< ...[more]

PMID: 26724471

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Project description:BackgroundRecent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.MethodsTwo hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.ResultsThere were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).ConclusionsAdjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

Project description:BACKGROUND:The treatment strategy for brain metastasis (BM) in patients with epidermal growth factor receptor (EGFR) -mutant lung adenocarcinoma (LAC) remains controversial. In the present study, we compared the efficacy of brain radiotherapy (RT) in combination with tyrosine kinase inhibitors (TKIs) and TKIs alone for advanced LAC patients with EGFR mutations and BM. METHODS:We retrospectively studied 78 patients diagnosed with EGFR-mutant LAC who developed BM. These patients were divided into two groups: 49 patients in the combination treatment group who received brain RT in combination with EGFR-TKIs (including 23 patients with asymptomatic BM before RT); 29 patients in the TKI group who received EGFR-TKI targeted therapy alone (including 22 patients with asymptomatic BM before TKI treatment). RESULTS:The median intracranial progression-free survival (iPFS) of the combination treatment group was longer than that of the TKI alone group (21.5 vs. 15?months; P?=?0.036). However, there were no significant differences in median progression-free survival (PFS, 12 vs. 13?months; P?=?0.242) and median overall survival (mOS, 36 vs. 23?months; P?=?0.363) between the two groups. Further analysis of asymptomatic BM showed that both the median iPFS and the mOS of the combination treatment group were significantly longer than for the TKI alone group (iPFS, 21.5 vs. 14.8?months, P?=?0.026; mOS, 36 vs. 23?months, P?=?0.041). Cox multivariate regression analysis found no independent adverse predictors of iPFS in all patients. CONCLUSIONS:The synchronous combination of brain RT and TKIs was superior to EGFR-TKIs alone for EGFR-mutant LAC patients with BM. The combination treatment group exhibited longer iPFS, while the PFS and OS were not significantly different between the two groups. In addition, the combination treatment could result in better iPFS and OS in those with asymptomatic BM. Therefore, addition of brain RT was useful for intracranial metastatic lesions.

Dataset Information

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

Publications

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

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