李博，劉黎明

(蚌埠醫(yī)學(xué)院第一附屬醫(yī)院呼吸科，安徽 蚌埠 233000)

非小細(xì)胞肺癌腦轉(zhuǎn)移靶向藥物治療現(xiàn)狀

李博，劉黎明

(蚌埠醫(yī)學(xué)院第一附屬醫(yī)院呼吸科，安徽 蚌埠 233000)

非小細(xì)胞肺癌腦轉(zhuǎn)移發(fā)生率高，是肺癌致死率高的原因之一。目前分子靶向治療被認(rèn)為是非小細(xì)胞肺癌腦轉(zhuǎn)移治療的重要手段，被認(rèn)為是全腦放療、立體定向放療和化療之后肺癌腦轉(zhuǎn)移新的治療手段。近年來隨著腫瘤學(xué)的發(fā)展，分子靶向治療在非小細(xì)胞肺癌腦轉(zhuǎn)移治療方面是越來越重要。本文主要針對非小細(xì)胞肺癌腦轉(zhuǎn)移靶向治療現(xiàn)狀進(jìn)行述評。

非小細(xì)胞肺癌；腦轉(zhuǎn)移；靶向治療

肺癌在惡性腫瘤中死亡率最高，占腫瘤死亡人數(shù)的13%，每年新增180萬肺癌患者[1]。其中非小細(xì)胞肺癌占80%～85%，10%～25%的患者已發(fā)生腦轉(zhuǎn)移，40%～50%患者治療中發(fā)展為腦轉(zhuǎn)移[2]。腦轉(zhuǎn)移后患者中位生存期(OS)3～6個月[3]。NSCLC腦轉(zhuǎn)移患者傳統(tǒng)治療手段如下：(1)手術(shù)治療：手術(shù)治療有一定局限性，主要適合全身狀態(tài)好、肺部病灶已控制、無其他器官轉(zhuǎn)移的患者[4-5]。(2)全腦放療(WBRT)：WBRT是NSCLC腦轉(zhuǎn)移的標(biāo)準(zhǔn)治療[6]，能快速緩解神經(jīng)系統(tǒng)癥狀、提高患者生存期[7]，但生存質(zhì)量無明顯改變[8]。(3)立體定向放射治療(Stereotactic radiosurgery，SRS)：具有準(zhǔn)確定位、劑量聚集和神經(jīng)并發(fā)癥狀少等特點，患者生存期、生活質(zhì)量改善不顯著。(4)化療：傳統(tǒng)觀點認(rèn)為化療藥物與大分子蛋白結(jié)合后[分子量＞400 Da(道爾頓，Dalton，Da，D)是用來衡量原子或分子質(zhì)量的單位，它被定義為C12原子質(zhì)量的1/12)]很難通過血腦屏障[9]，這是化療效果欠佳的根源;有學(xué)者提出另一觀點，認(rèn)為肺癌腦轉(zhuǎn)移后血腦屏障有一定的破壞，同時臨床試驗證實：鉑類聯(lián)合培美曲塞等化療藥物，患者中位生存期(OS)延長3.0～6.0個月[10-12]?？傊畟鹘y(tǒng)治療手段一定程度上延長了生存時間，但療效有限、副反應(yīng)較大。隨著分子靶向藥物在臨床中的運用，給非小細(xì)胞肺癌腦轉(zhuǎn)移患者帶來了希望，以及分子生物學(xué)、腫瘤學(xué)快速發(fā)展，大數(shù)據(jù)在醫(yī)學(xué)中的運用，越來越多的非小細(xì)胞肺癌靶點基因被發(fā)現(xiàn)，相關(guān)靶向藥物的問世為NSCLC腦轉(zhuǎn)移患者治療帶來了新方向，本文就分子靶向藥物治療NSCLC腦轉(zhuǎn)移治療現(xiàn)狀進(jìn)行綜述。

1 表皮生長因子受體酪氨酸激酶抑(Epidermal growth factor receptor tyrosine kinase inhibitor，EGFR-TKI)

EGFR是一種跨膜受體，研究表明，EGFR在非小細(xì)胞肺癌患者中常常高度表達(dá)，因此EGFR突變基因成為EGFR-TKI治療基因靶點，目前EGFR-TKI已廣泛用于NSCLC患者的治療，其中亞洲、不吸煙、女性患者已取得良好效果[13]，代表藥物：吉非替尼(Gefitinib)、厄洛替尼(Erlotinb)。近年來有大量關(guān)于EGFR-TKI對NSCLC腦轉(zhuǎn)移治療的臨床報告，發(fā)現(xiàn)反應(yīng)率達(dá)80%，中位總生存期(Overall survival，OS)12.9～ 21.9個月，無進(jìn)展生存期(Progression free survival，PFS) 6.6～11.7個月(見表1)，相比WBRT、SRS、化療，患者OS、PFS明顯增加。但Gefitinib、Erlotinb在治療NSCLC腦轉(zhuǎn)移患者方面，長期是學(xué)者爭論的焦點。實驗證實，Gefitinib腦脊液濃度能達(dá)到血液治療濃度的1.3%[19]，Erlotinb腦脊液濃度能達(dá)到血液治療濃度的2.77%[20]，可能Erlotinb對患者獲益更大，總體上Gefitinib、Erlotinb透過血腦屏障仍較低，隨著二代EGFR-TKI藥物Afatinib的問世，Hoffknecht等[21]研究發(fā)現(xiàn)，Afatinib透過血腦屏障率較高，對Gefitinib和Erlotinb治療后進(jìn)展的NSCLC腦轉(zhuǎn)移患者是有效的；Hata等[22]臨床發(fā)現(xiàn)Erlotinb治療無效的NSCLC腦轉(zhuǎn)移患者，口服Afatinib(50 mg/d)2個月，發(fā)現(xiàn)腦部轉(zhuǎn)移病灶為PR。也許在不久的將來，更多EGFR-TKI藥物問世后，會為NSCLC腦轉(zhuǎn)移患者帶來福音。

表1 EGFR-TKIs治療NSCLC腦轉(zhuǎn)移患者的臨床試驗和研究

2 棘皮動物微管相關(guān)蛋白樣4間變性淋巴瘤激酶融合基因(Echinoderm microtubule associated protein like 4 anaplastic lymphoma kinase inhibitor，EML4-ALK)抑制劑

ML4-ALK是NSCLC中新發(fā)現(xiàn)的癌變驅(qū)動基因[23]，約3%～7%的NSCLC患者含有此癌變驅(qū)動基因，不與EGFR、K-ras、HER2及BRAF突變基因共存[24]。ALK抑制劑主要是通過與ALK、c-Met、ROS-1多靶點驅(qū)動基因結(jié)合，再與位于細(xì)胞膜內(nèi)側(cè)酪氨酸激酶ATP結(jié)合域相結(jié)合，達(dá)到阻斷該通路的信號傳導(dǎo)來實現(xiàn)腫瘤細(xì)胞生長抑制和凋亡[25]。目前代表藥物：克唑替尼(Crizotinib)，但學(xué)者發(fā)現(xiàn)Crizotinib腦脊液藥物濃度僅僅是血液濃度的0.26%[26-27]，對NSCLC腦轉(zhuǎn)移患者可能效果欠佳，但學(xué)者Nir Peled等[28]和Kinoshita等[29]報告的兩例臨床病案，口服Crizotinib后，顱內(nèi)轉(zhuǎn)移病灶前者完全緩解(CR)、后者部分緩解(PR)；學(xué)者Daniel等[30]臨床單臂實驗(n=888)，發(fā)現(xiàn)其中首次口服Crizotinib患者，顱內(nèi)病灶DCR 56%，顱內(nèi)病灶未進(jìn)展時間(TTP)7個月；而Crizotinib為二線治療患者，顱內(nèi)病灶DCR 62%，TTP 13.2個月，差異具有統(tǒng)計學(xué)意義，綜上所述，Crizotinib對NSCLC腦轉(zhuǎn)移患者是有效的，但克唑替尼的耐藥性和ALK野生型患者治療無效等問題也成為治療的瓶頸。第二代ALK抑制劑藥物：Ceritinib和Alectinib，不僅克服Crizotinib耐藥問題而且分子量偏小[31]，但Ceritinib在NSCLC腦轉(zhuǎn)移的臨床報告仍不多見；而學(xué)者Ajimizu等[32]報告臨床個案，發(fā)現(xiàn)Crizotinib治療無效后，口服Alectinib 300 mg，2次/d，兩周后顱內(nèi)轉(zhuǎn)移病灶完全緩解。也有學(xué)者Shirish等[33]研究發(fā)現(xiàn)，非小細(xì)胞肺癌腦轉(zhuǎn)移患者21人，口服Alectinib 600 mg/d，顱內(nèi)病灶有效率為52%，CR 6人，PR 5人，SD 8人，更令人興奮的是在動物模型實驗中，發(fā)現(xiàn)Alectinib在腦組織濃度達(dá)到血液治療濃度[34]，總之ALK抑制劑對NSCLC腦轉(zhuǎn)移是有效的。

3 血管內(nèi)皮生長因子(Vascular endothelial growth foctor，VEGF)拮抗劑

VEGF在惡性腫瘤血管中常常是高度表達(dá)，VEGF拮抗劑是通過與VEGF結(jié)合達(dá)到約束腫瘤新生血管生成，最終減少腫瘤細(xì)胞組織間的滲透壓，增加其他化療藥物向腫瘤組織內(nèi)的滲透，提高非小細(xì)胞肺癌治療效果[35-37]，代表藥物：貝伐珠單抗(Bevacizumab)。在治療非小細(xì)胞肺癌腦轉(zhuǎn)移方面，許多學(xué)者考慮到Bevacizumab有并發(fā)腦出血風(fēng)險，被排除在治療之外；近年來一個多中心、開放性、非隨機對照的大型臨床試驗[38-39]數(shù)據(jù)發(fā)現(xiàn)貝伐珠單抗是基本安全的、有效的，學(xué)者Kim等[40]報道的臨床個案，發(fā)現(xiàn)鉑類治療無效，聯(lián)合Bevacizumab后，患者顱內(nèi)轉(zhuǎn)移病灶PR。學(xué)者Benjamin Besse等[41]臨床Ⅱ期實驗發(fā)現(xiàn)，Bevacizumab聯(lián)合Carboplatin(卡鉑)和Paclitaxel(紫杉醇)，PFS=6.7個月，OS=16.0個月(95%Cl 5.7～7.1，P＜0.05)，差異具有統(tǒng)計學(xué)意義，總之Bevacizumab在非小細(xì)胞肺癌腦轉(zhuǎn)移患者是安全的、有效的。

4 血管內(nèi)皮生長因子受體2(Vascular endothelial growth factor receptor-2 VEGFR-2)拮抗劑

VEGFR-2拮抗劑是通過與VEGFR-2結(jié)合后阻斷血管生成，達(dá)到抑制腫瘤細(xì)胞快速生長和轉(zhuǎn)移的效果。代表藥物：雷莫蘆單抗(Ramucirumab)，關(guān)于Ramucirumab在非小細(xì)胞肺癌腦轉(zhuǎn)移的運用臨床報告仍不多見，但一項全球性、隨機性、雙盲的臨床Ⅲ期試驗研究[42]發(fā)現(xiàn)Ramucirumab在晚期非小細(xì)胞肺癌(含有腦轉(zhuǎn)移患者)治療上能延長患者PFS、OS，也許在不久的將來，更多VEGFR-2拮抗劑的問世，會為非小細(xì)胞肺癌腦轉(zhuǎn)移患者治療帶來希望。

5 靶向免疫治療

免疫靶向治療是通過與一種PD-1(抑制抗腫瘤免疫原性的免疫檢測點分子)抑制劑受體相結(jié)合，解除PD-1通路介導(dǎo)的對免疫應(yīng)答的抑制，達(dá)到抗腫瘤作用的治療方法[43-45]，已成為腫瘤治療的研究熱點，其中Nivolumab對晚期非小細(xì)胞肺癌治療在不斷增加[46-48]。一項全球性、多中心參與的隨機大型臨床實驗證明[49-50]，Nivolumab能延長PFS、OS，也許在不久的將來，更多免疫靶向藥物的問世會為非小細(xì)胞肺癌腦轉(zhuǎn)移患者治療帶來曙光。

6 展 望

靶向藥物在非小細(xì)胞肺癌腦轉(zhuǎn)移患者治療上取得一定效果，仍未完全達(dá)到人們的期望，也許在不久的將來，隨著腫瘤分子生物學(xué)的發(fā)展，最新的基因測序技術(shù)進(jìn)步和大數(shù)據(jù)在醫(yī)學(xué)中的運用，更多誘發(fā)非小細(xì)胞肺癌的突變基因被發(fā)現(xiàn)，相關(guān)靶向藥物問世后，那時人們可以根據(jù)自身情況選擇適合的靶點藥物，對患者進(jìn)行個體化治療，最終達(dá)到提高療效，使非小細(xì)胞肺癌腦轉(zhuǎn)移患者獲益。

[1]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics[J].CA Cancer J Clin,2015,65(2):87-108.

[2]Preusser M,Capper D,Ilhan-Mutlu A,et al.Brain metastases : pathobiology and emerging targeted therapies[J].Acta Neuropathol, 2012,123(2):205-222.

[3]Sperduto PW,Kased N,Roberge D,et al.Summary report on the graded prognostic assessment:an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases[J].J Clin Oncol,2012,30(4):419-425.

[4]Kozower BD,Larner JM,Detterbeck FC,et al.Special treatment issues-in-non-small cell lung cancer:Diagnosis and management of-lung cancer,3rd ed:American College of Chest Physicians evidence-based clinical practice guidelines[J].Chest,2013,143(5): 369-399.

[5]Ettinger DS,Akerley W,Jakobsen KR,et al.Non-small cell lung canner[J].J Natl Compr Canc Netw,2013,11:645-653.

[6]殷蔚伯,余子豪,徐國鎮(zhèn)等.腫瘤放射治療學(xué)[M].4版.北京:中國協(xié)和醫(yī)科大學(xué)出版社,2008:1200-1206.

[7]Li J,Bentzen SM,Renschler M,et al.Relationship between neurocognitive function and quality of life after whole brain radiotherapy in patients with brain metastasis[J].Int J Radiat Oncolbiolphys, 2008,71(1):64-70.

[8]Kim KH,Lee J,Lee JI,et al.Can up front systemic chemotherapy replace stereotactic radiosurgery or whole brain radiotherapy in the treatment of non-small cell lung cancer patients with asymptomatic brain metastases?[J].Lung Cancer,2010,68(2):258-263.

[9]Walbert T,Gilbert MR.The role of chemotherapy in the treatment of patients with brain metastases from solid tumors[J].J Clin Oncol, 2009,14(4):299-306.

[10]Barlesi F,Gervais R,Lena H,et al.Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer(NSCLC)with asymptomatic inoperable brain metastases:a multicenter phase II trial (GFPC 07-01)[J].Ann Oncol,2011,22(11):2466-2470.

[11]Bailon O,Chouahnia K,Augier A,et al.Up front association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma[J].Neuro Oncol,2012,14(4):491-495.

[12]Dinglin XX,Huang Y,Liu H,et al.Pemetrexed and cisplatin combination with concurrent whole brain radiotherapy in patients with brain metastases of lung adenocarcinoma:a single-arm phase II clinical trial[J].J Neurooncol,2013,112(3):461-466.

[13]Mok TS,Wu YL,Fujita S,et al.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J].N Engl J Med,2009,361(10): 947-957.

[14]Porta R,Sanchez-Torres JM,Paz-Ares L,et al.Brain metastases from lung cancer responding to erlotinib:the importance of EGFR mutation[J].Eur Respir J,2011,37(3):624-631.

[15]Park SJ,Kim HT,Lee DH,et al.Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation[J]. Lung Cancer,2012,77(3):556-560.

[16]Welsh JW,Komaki R,Amini A,et al.PhaseⅡtrial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer[J].J Clin Oncol,2013,31 (7):895-902.

[17]Iuchi T,Shingyoji M,Sakaida T,et al.Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma[J].Lung Cancer,2013,82 (2):282-287.

[18]Song Z,Zhang Y.Gefitinib and erlotinib for non-small cell lung cancer patients who fail to respond to radiotherapy for brain metastases [J].J Clin Neurosci,2014,21(4):591-595.

[19]Zhao J,Chen M,Zhong W,et al.Cerebrospinal fluid concentrations of-gefitinib in patients with lung adenocarcinoma[J].Clin Lung Cancer,2013,14(2):188-193.

[20]Togashi Y,Masago K,Masuda S,et al.Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer[J].Cancer Chemother Pharmacol,2012,70(3):399-405.

[21]Hoffknecht P,Tufman A,Wehler T,et al.Efficacy of the irreversible ErbB family blocker afatinib in epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor(TKI)-pretreated non-small-cell lung cancer patients with brain metastasesor leptomeningeal disease [J].J Thorac Oncol,2015,10(1):156-163.

[22]Hata A,Katakami N.Afatinib for erlotinib refractory brain metastases in a patient with EGFR-mutant non-small-cell lung cancer:Canhigh-affinity TKI substitute for high-dose TKI?[J].J Thorac Oncol, 2015,10(7):e65-66.

[23]Soda M,Choi YL,Soda M,et al.Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer[J].Nature, 2007,448(7153):561-566.

[24]Horn L,Pao W,Heo JY,et al.EML4-ALK:honing in on a new target in non-small cell lung cancer[J].J Clin Oncol,2009,27(26): 4232-4235.

[25]Kwak EL,Bang YJ,Kolesar JM,et al.Anaplastic lymphoma kinase inhibition in non-small cell lung cancer[J].N Engl J Med,2010,363 (18):1693-1703.

[26]Costa DB,Kobayashi S,Pandya SS,et al.CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib[J].J Clin Oncol, 2011,29(15):443-445.

[27]Falk AT,Poudenx M,Otto J,et al.Adenocarcinoma of the lung with miliary brain and pulmonary metastases with echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase translocation treated with crizotinib:a case report[J].Lung Cancer(Amsterdam,Netherlands),2012,78(3):282-284.

[28]Peled N,Zach L,Liran O,et al.Effective Crizotinib schedule for brain metastases in ALK rearrangement metastatic non small-cell lung cancer[J].J Thorac Oncol,2013,8(12):112-113.

[29]Kinoshita Y,Koga Y,Sakamoto A,et al.Long-lasting response to crizotinib in brain metastasesdueto EML4-ALK-rearranged non-small-cell lung cancer[J].BMJ Case Rep,2013,10(5):1136.

[30]Daniel B,Shaw AT,Ou SH,et al.Clinical experience with crizotinib in patients with advanced ALK-rearranged non small-cell lung cancer and brain metastases[J].J Clin Oncol,2015,33(17):1881-1888.

[31]Nishio M,Murakami H,Horiike A,et al.Phase I study of-Ceritinib (LDK378)in Japanese patients with advanced,anaplastic lymphoma kinase-rearranged non-small-cell lung cancer or other tumors[J].J Thorac Oncol,2015,10(7):1058-1066.

[32]Ajimizu H,Kim YH,Mishima M,et al.Rapid response of brain metastases to alectinib in a patient with non-small-cell lung cancer resistant to crizotinib[J].Med Oncol,2015,32(2):477.

[33]Kim YH,Mishima M.Bevacizumab in combination with chemotherapy or molecularly targeted agents for non-small cell lung cancer with brain metastases[J].J Thorac Oncol 2015,10(8):e76.

[34]Kodama T,Hasegawa M,Takanashi K,et al.Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases[J].Cancer Chemother Pharmacol,2014,74:1023-1028.

[35]郭楠楠,尉承澤,于長海,等.非小細(xì)胞肺癌個體化治療相關(guān)分子標(biāo)記物[J].中國肺癌雜志,2011,14(3):292-295.

[36]Nishino M,Cryer SK,Takanashi K,et al.Tumoral cavitation in patients with non small cell lung cancer treated with antiangiogenic therapy using bevacizumab[J].Cancer Imaging,2012,12:225-235.

[37]黃誠,張晶,柯明耀,等.貝伐單抗聯(lián)合化療治療晚期多程治療失敗后的非小細(xì)胞肺癌臨床觀察[J].中國癌癥雜志,2012,22(1):47-51.

[38]Dansin E,Cinieri S,Garrido P,et al.MO19390(SAiL):bleeding events in a phaseⅣstudy of first-line bevacizumab with chemotherapy in patients with advanced non squamous NSCLC[J].Lung Cancer,2012,76(3):373-379.

[39]趙肖,王孟昭.貝伐珠單抗聯(lián)合紫杉醇/卡鉑治療晚期非小細(xì)胞肺癌25例分析[J].中國肺癌雜志,2012,15(1):6-10.

[40]Kim YH,Mishima M.Bevacizumab in combination with chemotherapy or molecularly targeted agents for non-smallcelllung cancer with brain metastases[J].J Thorac Oncol,2015,10(8):e76.

[41]Besse B,Le Moulec S,Mazières J,et al.Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic,untreated brain metastases(BRAIN):A Nonrandomized,Phase II Study [J].Clin Cancer Res,2015,21(8):1896-1903.

[42]Garon EB,Ciuleanu TE,Arrieta O,et al.Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy(REVEL):a multicentre,double-blind,randomised phase 3 trial[J].Lancet,2014,384(9944):665-673.

[43]Pardoll DM.The blockade of immune checkpoints in cancer immunotherapy[J].Nat Rev Cancer,2012,12(4):252-264.

[44]Waqar SN,Morgensztern D.Immunotherapy for non-small cell lung cancer:are we on the cusp of a new era?[J].Expert Rev Clin Immunol,2015,11(8):871-883.

[45]Brahmer JR,Drake CG,Wollner I,et al.PhaseⅠstudy of single-agent anti-programmed death-1(MDX-1106)in refractory solid tumors:safety,clinical activity,pharmacodynamics,andimmunologic correlates[J].J Clin Oncol,2010,28:3167-3175.

[46]Topalian SL,Hodi FS.Safety,activity,and immune correlates of anti-PD1 anti-body in cancer[J].N Engl J Med,2012,366:2443-2454.

[47]Rangachari D,Brahmer JR.Targeting the immune system in the treatment of non-small-cell lung cancer[J].Curr Treat Options Oncol,2013,14(4):580-594.

[48]Guilleminault L,Carmier D,Heuzé-Vourc'h,et al.Immunotherapy in non-small cell lung cancer:inhibition of PD1/PDL1 pathway[J].Rev Pneumol Clin,2015,71(1):44-56.

[49]Brahmer J,Reckamp KL,Baas P,et al.Nivolumab versus Docetaxel in advanced squamous-cell non-small-cell lung cancer[J].N Engl J Med,2015,373(2):123-135.

[50]Rizvi NA,Mazières J,Planchard D,et al.Activity and safety of nivolumab,an anti-PD-1 immune checkpoint inhibitor,for patients with advanced,refractory squamous non-small-cell lung cancer(Check-Mate 063):a phase 2,single-arm trial[J].Lancet Oncol,2015,16: 257-265.

Current situation of targeted therapy of brain metastases from non-small-cell lung cancer.

LI Bo,LIU Li-ming. Department of Respiratory Medicine,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,Anhui,CHINA

Brain metastases,with high incidence,are the main cause of high mortality in non-small cell lung cancer(NSCLC).Targeted therapy has become an important treatment for brain metastases from NSCLC after whole-brain radiation therapy,stereotactic radiosurgery and chemotherapy.In recent years,with the development of oncology,targeted therapy is becoming more and more important.This review mainly summarizes the current situation of targeted therapy in the treatment of brain metastases from NSCLC.

Non-small cell lung cancer(NSCLC);Brain metastases;Targeted therapy

R734.2

A

1003—6350（2016）09—1477—04

10.3969/j.issn.1003-6350.2016.09.035

2015-07-22)

劉黎明。E-mail：bbmcllm@126.com。