Treatment strategies of EGFR-mutated non-small cell lung cancer with brain metastases

doi:10.3760/cma.j.issn.1673-422X.2017.04.014

Abstract

Abstract: As the leading cause of death among lung cancer patients, brain metastasis occurs in approximately 10 percent of non-small cell lung cancer (NSCLC) patients at first diagnosis. Wholebrain radiation therapy (WBRT) is still the standard treatment for patients with brain metastasis, however, the efficacy of WBRT reaches a plateau. It has been proved that tyrosine kinase inhibitors (TKIs) make considerable therapeutic effect for NSCLC patients with brain metastasis. The combination therapy of TKIs with WBRT may provide new major treatment for epidermal growth factor receptor (EGFR) mutant NSCLC with brain metastasis.

Key words: Carcinoma, non-small-cell lung, Therapy, Metastasis, Epidermal growth factor receptor

Zhang Huibo, Li Xiangpan, Song Qibin. Treatment strategies of EGFR-mutated non-small cell lung cancer with brain metastases[J]. Journal of International Oncology, 2017, 44(4): 294-296.

References

［1］ Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016［J］. CA Cancer J Clin, 2016, 66(1): 7-30. DOI: 10.3322/caac.21332. ［2］ Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016［J］. CA Cancer J Clin, 2016, 66(4): 271-289. DOI: 10.3322/caac.21349. ［3］ Khuntia D, Brown P, Li J, et al. Wholebrain radiotherapy in the management of brain metastasis［J］. J Clin Oncol, 2006, 24(8): 1295-1304. DOI: 10.1200/JCO.2005.04.6185. ［4］ Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase Ⅲ, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)［J］. J Clin Oncol, 2011, 29(21): 2866-2874. DOI: 10.1200/JCO.2010.33.4235. ［5］ Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial［J］. Lancet Oncol, 2012, 13(3): 239-246. DOI: 10.1016/S1470-2045(11)70393X. ［6］ Mak RH, Doran E, Muzikansky A, et al. Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC［J］. Oncologist, 2011, 16(6): 886-895. DOI: 10.1634/theoncologist.2011-0040. ［7］ Iuchi T, Shingyoji M, Itakura M, et al. Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations［J］. Int J Clin Oncol, 2015, 20(4): 674-679. DOI: 10.1007/s10147-014-0760-9. ［8］ Luo YH, Wu CH, Huang CY, et al. Brain metastasis features and association with tumor epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung［J］. Asia Pac J Clin Oncol, 2016, In press. DOI: 10.1111/ajco.12576. ［9］ Han G, Bi J, Tan W, 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. ［10］ Zhuang H, Yuan Z, Wang J, 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. ［11］ El Gantery MM, Abd El Baky HM, El Hossieny HA, et al. Management of brain metastases with stereotactic radiosurgery alone versus whole brain irradiation alone versus both［J］. Radiat Oncol, 2014, 9: 116. DOI: 10.1186/1748-717X-9-116. ［12］ Aoyama H, Tago M, Shirato H. Stereotactic radiosurgery with or without wholebrain radiotherapy for brain metastases: secondary analysis of the JROSG 99-1 randomized clinical trial［J］. JAMA Oncol, 2015, 1(4): 457-464. DOI: 10.1001/jamaoncol.2015.1145. ［13］ Gow CH, Chien CR, Chang YL, et al. Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response［J］. Clin Cancer Res, 2008, 14(1): 162-168. DOI: 10.1158/1078-0432.CCR-07-1468. ［14］ Hsiao S, Lin H, Chou Y, 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. ［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. DOI: 10.1016/j.lungcan.2012.05.092. ［16］ 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. DOI: 10.1183/09031936.00195609. ［17］ Heon S, Yeap BY, Lindeman NI, et al. The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations［J］. Clin Cancer Res, 2012, 18(16): 4406-4414. DOI: 10.1158/1078-0432.CCR-12-0357. ［18］ Zeng YD, Liao H, Qin T, et al. Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy［J］. Oncotarget, 2015, 6(10): 8366-8376. DOI: 10.18632/oncotarget.3187. ［19］ Provencio M, Sánchez A, Garrido P, et al. New molecular targeted therapies integrated with radiation therapy in lung cancer［J］. Clin Lung Cancer, 2010, 11(2): 91-97. DOI: 10.3816/CLC.2010.n.012. ［20］ Zeng YD, Zhang L, Liao H, et al. Gefitinib alone or with concomitant whole brain radiotherapy for patients with brain metastasis from non-small-cell lung cancer: a retrospective study［J］. Asian Pac J Cancer Prev, 2012, 13(3): 909-914. ［21］ Chen Y, Yang J, Li X, et al. Firstline epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor alone or with whole-brain radiotherapy for brain metastases in patients with EGFR-mutated lung adenocarcinoma［J］. Cancer Sci, 2016, 107(12): 1800-1805. DOI: 10.1111/cas.13079. ［22］ 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 Phy, 2016, 95(2): 673-679. DOI: 10.1016/j.ijrobp.2016.01.037. ［23］ Zhou L, He J, Xiong W, et al. Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: results of phase Ⅰ doseescalation study［J］. Lung Cancer, 2016, 96: 93-100. DOI: 10.1016/j.lungcan.2016.04.003.

[1]	Qian Xiaotao, Shi Ziyi, Hu Ge, Wu Xiaowei. Efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma： a real-world clinical study [J]. Journal of International Oncology, 2024, 51(6): 326-331.
[2]	Yang Mi, Bie Jun, Zhang Jiayong, Deng Jiaxiu, Tang Zuge, Lu Jun. Analysis of the efficacy and prognosis of neoadjuvant therapy for locally advanced resectable esophageal cancer [J]. Journal of International Oncology, 2024, 51(6): 332-337.
[3]	Zhang Baihong, Yue Hongyun. Advances in anti-tumor drugs with new mechanisms of action [J]. Journal of International Oncology, 2024, 51(6): 354-358.
[4]	Xu Fenglin, Wu Gang. Research progress of EBV in tumor immune microenvironment and immunotherapy of nasopharyngeal carcinoma [J]. Journal of International Oncology, 2024, 51(6): 359-363.
[5]	Wang Ying, Liu Nan, Guo Bing. Advances of antibody-drug conjugate in the therapy of metastatic breast cancer [J]. Journal of International Oncology, 2024, 51(6): 364-369.
[6]	Gao Fan, Wang Ping, Du Chao, Chu Yanliu. Research progress on intestinal flora and non-surgical treatment of the colorectal cancer [J]. Journal of International Oncology, 2024, 51(6): 376-381.
[7]	Fan Zhipeng, Yu Jing, Hu Jing, Liao Zhengkai, Xu Yu, Ouyang Wen, Xie Conghua. Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy [J]. Journal of International Oncology, 2024, 51(5): 257-266.
[8]	Wang Junyi, Hong Kaibin, Ji Rongjia, Chen Dachao. Effect of cancer nodules on liver metastases after radical resection of colorectal cancer [J]. Journal of International Oncology, 2024, 51(5): 280-285.
[9]	Wang Peixin, Zhao Jun, Xu Shihong, Jiang Zhaoyang, Wang Xiaoqiang, Yang Hongjuan. Progress of ferroptosis-related mechanisms in osteosarcoma [J]. Journal of International Oncology, 2024, 51(5): 308-311.
[10]	Yang Hao, Shi Guidong, Zhang Chengcheng, Zhang Yue, Zhang Liwen, Fu Maoyong. Comparison of efficacy and safety between sintilimab and tislelizumab in neoadjuvant therapy for advanced esophageal squamous cell carcinoma [J]. Journal of International Oncology, 2024, 51(4): 210-216.
[11]	Sa Qiang, Xu Hangcheng, Wang Jiayu. Advances in immunotherapy for breast cancer [J]. Journal of International Oncology, 2024, 51(4): 227-234.
[12]	Yang Zhi, Lu Yiqiao, Gu Huayan, Ding Jialing, Guo Guilong. Research progress of tumor microenvironment mediated drug resistance in targeted therapy of breast cancer [J]. Journal of International Oncology, 2024, 51(4): 235-238.
[13]	Sun Weiwei, Yao Xuemin, Wang Pengjian, Wang Jing, Jia Jinghao. Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes [J]. Journal of International Oncology, 2024, 51(3): 143-150.
[14]	Qian Xiaotao, Shi Ziyi, Hu Ge. A real-world clinical study of immunocheckpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy in stage Ⅲ-ⅣA esophageal squamous cell carcinoma [J]. Journal of International Oncology, 2024, 51(3): 151-156.
[15]	Li Shuyue, Ma Chenying, Zhou Juying, Xu Xiaoting, Qin Songbing. Progress of radiotherapy in oligometastatic non-small cell lung cancer [J]. Journal of International Oncology, 2024, 51(3): 170-174.