Research progress in tyrosine kinase inhibitor combined with radiotherapy for brain metastases in patients with non-small cell lung cancer
Kong Yue,Song Zhenbo,Chen Ming
Department of Radiation Oncology,Zhejiang Cancer Hospital,Zhejiang Key Laboratory of Radiation Oncology,Hangzhou 310022,China (Kong Y,Chen M);Department of Chemotherapy,Zhejiang Cancer Hospital,Hangzhou 310022,China (Song ZB)
Abstract： Brain metastases (BM) are a frequent complication of non-small cell lung cancer (NSCLC), with various treatment strategies. The widespread use of tyrosine kinase inhibitor (TKI) has significantly prolonged the survival of NSCLC patients with epidermal growth factor receptor mutations. This article reviews recent progress in TKI therapy for BM in NSCLC patients and discusses a combination of TKI and radiotherapy.
Kong Yue,Song Zhenbo,Chen Ming. Research progress in tyrosine kinase inhibitor combined with radiotherapy for brain metastases in patients with non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2017, 26(10): 1218-1221.
[1] Barnholtz-Sloan JS,Sloan AE,Davis FG,et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan detroit cancer surveillance system[J].J Clin Oncol,2004,22(14):2865-2872.DOI:10.1200/JCO.2004.12.149. [2] Gaspar L,Scott C,Rotman M,et al. Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials[J].Int J Radiat Oncol Biol Phys,1997,37(4):745-751.DOI:10.1016/S0360-3016(96)00619-0. [3] Sperduto PW,Berkey B,Gaspar LE,et al. A new prognostic index and comparison to three other indices for patients with brain metastases:an analysis of 1,960 patients in the RTOG database[J].Int J Radiat Oncol Biol Phys,2008,70(2):510-514.DOI:10.1016/j.ijrobp.2007.06.074. [4] Sperduto PW,Chao ST,Sneed PK,et al. Diagnosis-specific prognostic factors,indexes,and treatment outcomes for patients with newly diagnosed brain metastases:a multi-institutional analysis of 4,259 patients[J].Int J Radiat Oncol Biol Phys,2010,77(3):655-661.DOI:10.1016/j.ijrobp.2009.08.025. [5] Hsiao SH,Lin HC,Chou YT,et al. Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients[J].Lung Cancer,2013,81(3):455-461.DOI:10.1016/j.lungcan.2013.06.004. [6] Li HW,Zhang XQ,Cao JZ,et al. Exon 19 deletion of epidermal growth factor receptor is associated with prolonged survival in brain metastases from non-small-cell lung cancer[J].Tumor Biol,2015,36(12):9251-9258.DOI:10.1007/s13277-015-3653-2. [7] Lee HL,Chung TS,Ting LL,et al. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases[J].Radiat Oncol,2012,7:181.DOI:10.1186/1748-717X-7-181. [8] Eichler AF,Kahle KT,Wang DL,et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer[J].Neuro-Oncology,2010,12(11):1193-1199.DOI:10.1093/neuonc/noq076. [9] Lee DW,Shin DY,Kim JW,et al. Additional prognostic role of EGFR activating mutations in lung adenocarcinoma patients with brain metastasis:integrating with lung specific GPA score[J].Lung Cancer,2014,86(3):363-368.DOI:10.1016/j.lungcan.2014.10.001. [10] Shin DY,Na Ⅱ,Kim CH,et al. EGFR mutation and brain metastasis in pulmonary adenocarcinomas[J].J Thorac Oncol,2014,9(2):195-199.DOI:10.1097/JTO.0000000000000069. [11] Hsu F,De Caluwe A,Anderson D,et al. EGFR mutation status on brain metastases from non-small cell lung cancer[J].Lung Cancer,2016,96:101-107.DOI:10.1016/j.lungcan.2016.04.004. [12] Han G,Bi JP,Tan WY,et al. A retrospective analysis in patients with EGFR-mutant lung adenocarcinoma:is EGFR mutation associated with a higher incidence of brain metastasis?[J].Oncotarget,2016,7(35):56998-57010.DOI:10.18632/oncotarget.10933. [13] Daniele L,Cassoni P,Bacillo E,et al. Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer[J].J Thorac Oncol,2009,4(6):684-688.DOI:10.1097/JTO.0b013e3181a52359. [14] Luo D D,Ye X,Hu Z,et al. EGFR mutation status and its impact on survival of Chinese non-small cell lung cancer patients with brain metastases[J].Tumour Biol,2014,35(3):2437-2444.DOI:10.1007/s13277-013-1323-9. [15] Rau KM,Chen HK,Shiu LY,et al. Discordance of mutation statuses of epidermal growth factor receptor and K-ras between primary adenocarcinoma of lung and brain metastasis[J].Int J Mol Sci,2016,17(4):524.DOI:10.3390/ijms17040524. [16] Weber B,Winterdahl M,Memon A,et al. Erlotinib accumulation in brain metastases from non-small cell lung cancer:visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor[J].J Thorac Oncol,2011,6(7):1287-1289.DOI:/10.1097/JTO.0b013e318219ab87. [17] Togashi Y,Masago K,Fukudo M,et al. Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation[J].Cancer Chemother Pharmacol,2011,68(4):1089-1092.DOI:10.1007/s00280-011-1691-z. [18] Clarke JL,Pao W,Wu N,et al. High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer[J].J Neuro Oncol,2010,99(2):283-286.DOI:10.1007/s11060-010-0128-6. [19] Jackman DM,Holmes AJ,Lindeman N,et al. Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib[J].J Clin Oncol,2006,24(27):4517-4520.DOI:10.1200/JCO.2006.06.6126. [20] Grommes C,Oxnard GR,Kris MG,et al.“Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer[J].Neuro Oncol,2011,13(12):1364-1369.DOI:10.1093/neuonc/nor121. [21] Greig SL.Osimertinib:first global approval[J].Drugs,2016,76(2):263-273.DOI:10.1007/s40265-015-0533-4. [22] Ballard P,Yates JWT,Yang ZF,et al. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models,and early evidence of clinical brain metastases activity[J].Clin Cancer Res,2016,22(20):5130-5140.DOI:10.1158/1078-0432.CCR-16-0399. [23] Zeng QB,Wang JB,Cheng ZQ,et al. Discovery and evaluation of clinical candidate AZD3759,a potent,oral active,central nervous system-penetrant,epidermal growth factor receptor tyrosine kinase inhibitor[J].J Med Chem,2015,58(20):8200-8215.DOI:10.1021/acs.jmedchem.5b01073. [24] Yang JCH,Kim DW,Kim SW,et al. Osimertinib activity in patients (pts) with leptomeningeal (LM) disease from non-small cell lung cancer (NSCLC):updated results from BLOOM,a phase I study[J].J Clin Oncol,2016,34(Suppl 1):9002. [25] Ahn MJ,Arbour KC,Riely GJ,et al. Phase I study of AZD3759,a CNS penetrable EGFR inhibitor,for the treatment of non-small-cell lung cancer (NSCLC) with brain metastasis (BM) and leptomeningeal metastasis (LM)[J].J Clin Oncol,2016,34(Suppl 1):9003. [26] Wu YL,Zhou C,Cheng Y,et al. Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases:a phase Ⅱ study (CTONG-0803)[J].Ann Oncol,2013,24(4):993-999.DOI:10.1093/annonc/mds529. [27] Schuler M,Wu YL,Hirsh V,et al. First-line afatinib versus chemotherapy in patients with non–small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases[J].J Thorac Oncol,2016,11(3):380-390.DOI:10.1016/j.jtho.2015.11.014. [28] 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.DOI:10.1016/j.lungcan.2013.08.016. [29] Soon YY,Leong CN,Koh WY,et al. EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases:a systematic review and meta-analysis[J].Radiother Oncol,2015,114(2):167-172.DOI:10.1016/j.radonc.2014.12.011. [30] Jiang T,Min WJ,Li YN,et al. Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases:an update meta-analysis[J].Cancer Med,2016,5(6):1055-1065.DOI:10.1002/cam4.673. [31] Magnuson WJ,Yeung JT,Guillod PD,et al. Impact of deferring radiation therapy in patients with epidermal growth factor receptor–mutant non-small cell lung cancer who develop brain metastases[J].Int J Radiat Oncol Biol Phys,2016,95(2):673-679.DOI:10.1016/j.ijrobp.2016.01.037. [32] Fan Y,Huang ZY,Fang L,et al. A phase Ⅱ study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer[J].Cancer Chemother Pharmacol,2015,76(3):517-523.DOI:10.1007/s00280-015-2760-5. [33] Welsh JW,Komaki R,Amini A,et al. Phase Ⅱ trial 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.DOI:10.1200/JCO.2011.40.1174. [34] Lu YY,Fan Y.Combined action of EGFR tyrosine kinase inhibitors and whole-brain radiotherapy on EGFR-mutated non-small-cell lung cancer patients with brain metastasis[J].Onco Targets Ther,2016,9:1135-1143.DOI:10.2147/OTT.S95871. [35] 刘桂梅,张新勇,田翠孟,等.全脑放疗时间对EGFR突变非小细胞肺癌脑转移患者生存的影响[J].中国肺癌杂志,2016,19(8):501-507.DOI:10.3779/j.issn.1009-3419.2016.08.03. Liu GM,Zhang XY,Tian CM,et al. Timing of whole brain radiotherapy on survival of patients with EGFR-mutated non-small cell lung cancer and brain metastases[J].Chin J Lung Cancer,2016,19(8):501-507.DOI:10.3779/j.issn.1009-3419.2016.08.03. [36] Cai L,Zhu JF,Zhang XW,et al. A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer[J].J Neuro Oncol,2014,120(2):423-430.DOI:10.1007/s11060-014-1570-7. [37] Zhuang HQ,Yuan ZY,Wang P,et al. Phase Ⅱ study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma[J].Drug Des Devel Ther,2013,7:1179-1186.DOI:10.2147/DDDT.S53011. [38] Lee SM,Lewanski CR,Counsell N,et al. Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases[J].J Natl Cancer Inst,2014,106(7):dju151.DOI:10.1093/jnci/dju151.
2017, Vol. 26 
