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Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases: an update meta-analysis.

ABSTRACT: Brain metastasis (BM) is the common complication of non-small cell lung cancer (NSCLC) with a poor prognosis and dismal survival rate. This update meta-analysis aimed to derive a more precise estimation of radiotherapy plus epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC patients with BM. PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Library were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using STATA Version 12.0. In total, 15 studies involving 1552 participants were included. The results indicated that radiotherapy plus EGFR TKIs was more effective at improving response rate and disease control rate (DCR) (risk ratio (RR) = 1.48, 95% confidence interval [CI]: 1.12-1.96, P = 0.005; RR = 1.29, 95% CI: 1.02-1.60, P = 0.035; respectively) than radiotherapy alone or plus chemotherapy. Moreover, radiotherapy plus EGFR TKIs significantly prolonged the time to central nervous system progression (CNS-TTP) (HR = 0.56, 95% CI [0.33, 0.80]; P = 0.000) and median overall survival (OS) (HR = 0.58, 95% CI [0.42, 0.74]; P = 0.000) but significantly increased adverse events (any grade) (RR = 1.25, 95% CI [1.01, 1.57]; P = 0.009), especially rash and dry skin. These results suggested that radiotherapy plus EGFR TKIs produced superior response rate and DCR and markedly prolonged the CNS-TTP and OS of NSCLC patients with BM. However, combined groups had the higher rate of incidence of overall adverse effects, especially rash and dry skin.

SUBMITTER: Jiang T

PROVIDER: S-EPMC4924363 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases: an update meta-analysis.

Jiang Tao T Min Weijie W Li Yanan Y Yue Zhijian Z Wu Chunyan C Zhou Caicun C

Cancer medicine 20160314 6

Brain metastasis (BM) is the common complication of non-small cell lung cancer (NSCLC) with a poor prognosis and dismal survival rate. This update meta-analysis aimed to derive a more precise estimation of radiotherapy plus epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC patients with BM. PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Library were searched to identify any relevant publications. After screening the literature and undertaking qualit ...[more]

PMID: 26990668

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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.

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.

Dataset Information

Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases: an update meta-analysis.

Publications

Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases: an update meta-analysis.

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