Abstract
Brain metastases account for the majority of malignant brain tumors and as newer cancer treatments improve patient survival, the reported incidence of brain metastases is increasing. Lung cancer is the most frequent origin of metastases to the brain, and this diagnosis is associated with significant morbidity as well as decreased quality of life and a worse prognosis. The treatment for brain metastases in NSCLC has historically been local therapy, either surgery or radiation, as many chemotherapies have limited efficacy in the brain. These strategies are highly effective but can be a source of morbidity themselves. Newer systemic therapies, including targeted small molecule drugs and immunotherapy, have shown promise in treating NSCLC associated CNS disease either alone or in combination with local therapies. Increasing evidence for this strategy is accumulating as more clinical trials allow the inclusion of patients with untreated asymptomatic brain metastases. This chapter summarizes the current use of systemic therapy in the treatment of brain metastases in NSCLC.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Svokos KA, Salhia B, Toms SA (2014) Molecular biology of brain metastasis. Int J Mol Sci 15(6):9519–9530
Peters S et al (2016) The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer. Cancer Treat Rev 45:139–162
Laurie Gaspar, C.S.M, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive Partition Analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751
Cagney DN et al (2017) Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro-Oncology 19(11):1511–1521
Kromer C et al (2017) Estimating the annual frequency of synchronous brain metastasis in the United States 2010-2013: a population-based study. J Neuro-Oncol 134(1):55–64
Barnholtz-Sloan JS et al (2004) Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 22(14):2865–2872
Brown PD, MSA, Kahn OH, Asher AL, Wefel JS, Gondi V (2018) Whole brain radiotherapy for brain metastases: evolution or revolution. J Clin Oncol 36:483
<Weinberg2001_Article_SurgicalManagementOfBrainMetas.pdf>
Grant FC (1926) Concerning Intrcranial malignant metastases: their frequency and the value of surgery in their treatment. Ann Surg 84:635–646
Narayan Sundaresan JHG (1985) Surgical treatment of brain metastases. Cancer 55:1382–1388
Markesbery WR, Brooks WH, Gupta GD, Young AB (1978) Treatment for patients with cerebral metastases. JAMA Neurol 35:754–756
Mandell L et al (1986) The treatment of single brain metastasis from non-oat cell lung carcinoma. Surgery and radiation versus radiation therapy alone. Cancer 58(3):641–649
White KT, Fleming TR, Laws ER Jr (1981) Single metastasis to the brain. Surgical treatment in 122 consecutive patients. Mayo Clin Proc 56(7):424–428
Bindal RK et al (1993) Surgical treatment of multiple brain metastases. J Neurosurg 79(2):210–216
Mintz AH et al (1996) A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 78(7):1470–1476
Brown PD et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316(4):401–409
Jen-Hung Chao, RP, Nickson JJ (1954) Roentgen-ray therapy of cerebral metastases. Cancer 7:682–689
Borgelt BGR, Kramer S, Brady LW, Chang CH, Davis LW, Perez CA, Hendrickson FR (1980) The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 6:1
Sneed PK, Larson DA, Wara WM (1996) Radiotherapy for cerebral metastases. Neurosurg Clin N Am 7(3):505–516
Katz HR (1981) The relative effectiveness of radiation therapy, corticosteroids, and surgery in the management of melanoma metastatic to the central nervous system. Int J Radiat Oncol Biol Phys 7(7):897–906
Hussain A et al (2007) Stereotactic radiosurgery for brainstem metastases: survival, tumor control, and patient outcomes. Int J Radiat Oncol Biol Phys 67(2):521–524
Tallet AV et al (2012) Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol 7:77
Schimmel WCM et al (2018) Cognitive effects of stereotactic radiosurgery in adult patients with brain metastases: a systematic review. Adv Radiat Oncol 3(4):568–581
Minniti G et al (2011) Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 6:48
Chin LS, Ma L, DiBiase S (2001) Radiation necrosis following gamma knife surgery: a case-controlled comparison of treatment parameters and long-term clinical follow up. J Neurosurg 94(6):899–904
Network, N.C.C. Small cell lung cancer (version 1.2021. 2020 November 15, 2020]; Available from: https://www.nccn.org/professionals/physician_gls/pdf/sclc_blocks.pdf
Ribatti D et al (2006) Development of the blood-brain barrier: a historical point of view. Anat Rec B New Anat 289(1):3–8
Saunders NR et al (2014) The rights and wrongs of blood-brain barrier permeability studies: a walk through 100 years of history. Front Neurosci 8:404
Fricker G et al (2014) The Blood Brain Barrier (BBB). Springer, Berlin, Heidelberg
Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr Neuropharmacol 6(3):179–192
Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28(1):12–18
Louveau A et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337–341
Cserr HF, Harling-Berg CJ, Knopf PM (1992) Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol 2(4):269–276
Kida S, Pantazis A, Weller RO (1993) CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 19(6):480–488
Wekerle H, Sun DM (2010) Fragile privileges: autoimmunity in brain and eye. Acta Pharmacol Sin 31(9):1141–1148
Berghoff AS et al (2016) Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC). J Neuro-Oncol 130(1):19–29
Kamath SD, Kumthekar PU (2018) Immune checkpoint inhibitors for the treatment of Central Nervous System (CNS) metastatic disease. Front Oncol 8:414
Goldberg SB et al (2016) Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol 17(7):976–983
Goldberg SB et al (2020) Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Lancet Oncol 21(5):655–663
Vittorio Franciosi GCM, Michiara M, Di Constanzo F, Fosser V, Tonato M, Carlini P, Boni C, Di Sarra S (1999) Front-line chemotheraphy with Cisplatin and Etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma. Cancer 85:1599–1605
Bailon O et al (2012) Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma. Neuro-Oncology 14(4):491–495
Cortes J et al (2003) Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology 64(1):28–35
Fujita A et al (2000) Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer. Oncology 59(4):291–295
Quadvlieg V et al (2004) Frontline gemcitabine and cisplatin based chemotherapy in patients with NSCLC inoperable brain metastases. J Clin Oncol 22(14_suppl):7117
Bearz A et al (2010) Activity of Pemetrexed on brain metastases from non-small cell lung cancer. Lung Cancer 68(2):264–268
Ardizzoni A et al (1997) Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for research and treatment of cancer early clinical studies group and new drug development office, and the lung cancer cooperative group. J Clin Oncol 15(5):2090–2096
Korfel A, O.C, von Pawel J, Keppler U, Deppermann M, Kaubitsch S, Thiel E (2002) Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation. A multicentre phase II study. Eur J Cancer 38:1724–1729
Qin H et al (2014) Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis. PLoS One 9(10):e111475
Sandler A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550
Besse B et al (2015) Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic, untreated Brain metastases (BRAIN): a nonrandomized, phase II study. Clin Cancer Res 21(8):1896–1903
Barlesi F et al (2016) Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 387(10026):1415–1426
Kris MG et al (2014) Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311(19):1998–2006
Shi Y et al (2014) A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 9(2):154–162
Iuchi T et al (2015) Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations. Int J Clin Oncol 20(4):674–679
Shin DY et al (2014) EGFR mutation and brain metastasis in pulmonary adenocarcinomas. J Thorac Oncol 9(2):195–199
Omuro AM et al (2005) High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 103(11):2344–2348
Deng Y et al (2014) The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer. Mol Clin Oncol 2(1):116–120
Masuda T et al (2011) Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 67(6):1465–1469
Porta R et al (2011) Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 37(3):624–631
Wu YL et al (2013) Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG-0803). Ann Oncol 24(4):993–999
Park SJ et al (2012) 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. Lung Cancer 77(3):556–560
Zhao J et al (2013) Cerebrospinal fluid concentrations of gefitinib in patients with lung adenocarcinoma. Clin Lung Cancer 14(2):188–193
Zhang Q et al (2016) Effects of epidermal growth factor receptor-tyrosine kinase inhibitors alone on EGFR-mutant non-small cell lung cancer with brain metastasis. Thorac Cancer 7(6):648–654
Ma S et al (2009) Treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and Gefitinib in a Chinese population. Lung Cancer 65(2):198–203
Iuchi T et al (2013) Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma. Lung Cancer 82(2):282–287
Ceresoli GL et al (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 15(7):1042–1047
Wu C et al (2007) Gefitinib in the treatment of advanced non-small cell lung cancer with brain metastasis. Zhonghua Zhong Liu Za Zhi 29(12):943–945
Hata A et al (2015) Spatiotemporal T790M heterogeneity in individual patients with EGFR-mutant non-small-cell lung cancer after acquired resistance to EGFR-TKI. J Thorac Oncol 10(11):1553–1559
Grommes C et al (2011) "Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro-Oncology 13(12):1364–1369
Yu HA et al (2017) Phase 1 study of twice weekly pulse dose and daily low-dose erlotinib as initial treatment for patients with EGFR-mutant lung cancers. Ann Oncol 28(2):278–284
Arbour KC et al (2018) Twice weekly pulse and daily continuous-dose erlotinib as initial treatment for patients with epidermal growth factor receptor-mutant lung cancers and brain metastases. Cancer 124(1):105–109
Sequist LV et al (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31(27):3327–3334
Wu Y-L et al (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15(2):213–222
Schuler M et al (2016) 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 Thorac Oncol 11(3):380–390
Hoffknecht P et al (2015) 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 metastases or leptomeningeal disease. J Thorac Oncol 10(1):156–163
Gerber NK et al (2014) Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma. Int J Radiat Oncol Biol Phys 89(2):322–329
Soon YY et al (2015) 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. Radiother Oncol 114(2):167–172
Magnuson WJ et al (2017) Management of brain metastases in tyrosine kinase inhibitor-naive epidermal growth factor receptor-mutant non-small-cell lung cancer: a retrospective multi-institutional analysis. J Clin Oncol 35(10):1070–1077
Soria JC et al (2018) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378(2):113–125
Network, N.C.C. Lung cancer (Version 7.2019). August 15., 2019]; Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf
Ballard P et al (2016) Preclinical comparison of Osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res 22(20):5130–5140
Mok TS et al (2017) Osimertinib or platinum-Pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 376(7):629–640
Goss G et al (2018) CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol 29(3):687–693
Yang JC-H et al (2017) Osimertinib for patients (pts) with leptomeningeal metastases (LM) from EGFR-mutant non-small cell lung cancer (NSCLC): updated results from the BLOOM study. J Clin Oncol 35(15_suppl):2020
Rodig SJ et al (2009) Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res 15(16):5216–5223
Rangachari D et al (2015) Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer 88(1):108–111
Costa DB et al (2015) Clinical experience with Crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol 33(17):1881–1888
Solomon BJ et al (2016) Intracranial efficacy of Crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol 34(24):2858–2865
Costa DB et al (2011) CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol 29(15):e443–e445
Kodama T et al (2014) Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases. Cancer Chemother Pharmacol 74(5):1023–1028
Gadgeel SM et al (2016) Pooled analysis of CNS response to Alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer. J Clin Oncol 34(34):4079–4085
Novello S et al (2018) Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol 29(6):1409–1416
Peters S et al (2017) Alectinib versus Crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 377(9):829–838
Lin JJ et al (2019) Efficacy of Alectinib in patients with ALK-positive NSCLC and symptomatic or large CNS metastases. J Thorac Oncol 14(4):683–690
Kim D-W et al (2016) Activity and safety of ceritinib in patients with ALK -rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol 17(4):452–463
Shaw AT et al (2017) Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 18(7):874–886
Soria J-C et al (2017) First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet 389(10072):917–929
Kim DW et al (2017) Brigatinib in patients with Crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol 35(22):2490–2498
Camidge DR et al (2018) Brigatinib versus Crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med 379(21):2027–2039
Shaw AT et al (2017) Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol 18(12):1590–1599
Solomon BJ et al (2018) Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol 19(12):1654–1667
Solomon B et al (2020) LBA2 Lorlatinib vs crizotinib in the first-line treatment of patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC): results of the phase III CROWN study. Ann Oncol 31:S1180–S1181
Goodman A Lorlatinib improves outcomes over Crizotinib in first-line setting of ALK-positive NSCLC: CROWN trial. In: The ASCO post 2020. HSP News Service, L.L.C
Selvaggi G et al (2020) ID:1882 phase III randomized study of Ensartinib vs Crizotinib in anaplastic lymphoma kinase (ALK) POSITIVE NSCLC patients: eXalt3. J Thorac Oncol 15(10):e41–e42
Solomon B et al (2017) OA 05.06 phase 2 study of Lorlatinib in patients with advanced ALK+/ROS1+ non-small-cell lung cancer. J Thorac Oncol 12(11):S1756
Lim SM et al (2017) Open-label, multicenter, phase II study of Ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol 35(23):2613–2618
Drilon A et al (2020) Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol 21(2):261–270
Drilon A et al (2018) Frequency of brain metastases and multikinase inhibitor outcomes in patients with RET-rearranged lung cancers. J Thorac Oncol 13(10):1595–1601
Lin JJ et al (2016) Clinical activity of Alectinib in advanced RET-rearranged non-small cell lung Cancer. J Thorac Oncol 11(11):2027–2032
Velcheti V et al (2017) OA 12.07 LOXO-292, a potent, highly selective RET inhibitor, in MKI-resistant RET fusion-positive lung cancer patients with and without brain metastases. J Thorac Oncol 12(11):S1778
Guo R et al (2019) Response to selective RET inhibition with LOXO-292 in a patient with RET fusion-positive lung cancer with leptomeningeal metastases. JCO Precis Oncol 3:1
Drilon A et al (2020) Efficacy of Selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 383(9):813–824
Falchook GS et al (2012) Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 379(9829):1893–1901
Davies MA et al (2017) Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 18(7):863–873
Planchard D et al (2016) Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 17(5):642–650
Planchard D et al (2016) Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 17(7):984–993
Planchard D et al (2017) Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol 18(10):1307–1316
Robinson SD et al (2014) BRAF V600E-mutated lung adenocarcinoma with metastases to the brain responding to treatment with vemurafenib. Lung Cancer 85(2):326–330
Yamamoto G et al (2019) Response of BRAF(V600E)-mutant lung adenocarcinoma with brain metastasis and leptomeningeal dissemination to Dabrafenib plus Trametinib treatment. J Thorac Oncol 14(5):e97–e99
Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264
Drugs FDA approved for lung cancer (2019, Sept 18) [cited 2019 October 10, 2019]; Available from: https://www.cancer.gov/about-cancer/treatment/drugs/lung#1
Hellmann MD et al (2019) Nivolumab plus Ipilimumab in advanced non-small-cell lung Cancer. N Engl J Med 381(21):2020–2031
Reck M et al (2020) Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. J Clin Oncol 38(15_suppl):9501
Reardon DA et al (2016) Glioblastoma eradication following immune checkpoint blockade in an orthotopic, immunocompetent model. Cancer Immunol Res 4(2):124–135
Berghoff AS, Preusser M (2018) New developments in brain metastases. Ther Adv Neurol Disord 11:1756286418785502
Borghaei H et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med 373(17):1627–1639
Goldman JW et al (2016) Nivolumab (nivo) in patients (pts) with advanced (adv) NSCLC and central nervous system (CNS) metastases (mets). J Clin Oncol 34(15_suppl):9038
Reck M et al (2016) Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell. Lung Cancer 375(19):1823–1833
Gandhi L et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092
Garassino MC et al (2019) Abstract CT043: outcomes among patients (pts) with metastatic nonsquamous NSCLC with liver metastases or brain metastases treated with pembrolizumab (pembro) plus pemetrexed-platinum: results from the KEYNOTE-189 study. 79(13 Supplement):CT043
Rittmeyer A et al (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389(10066):255–265
Gadgeel SM et al (2019) Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: exploratory analyses of the phase III OAK study. Lung Cancer 128:105–112
Lukas RV et al (2017) Safety and efficacy analyses of atezolizumab in advanced non-small cell lung cancer (NSCLC) patients with or without baseline brain metastases. Ann Oncol 28:1128
Crino L et al (2019) Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer. Lung Cancer 129:35–40
Cortinovis D et al (2019) Italian cohort of the Nivolumab EAP in squamous NSCLC: efficacy and safety in patients with CNS metastases. Anticancer Res 39(8):4265–4271
Molinier O et al (2017) OA 17.05 IFCT-1502 CLINIVO: real-life experience with Nivolumab in 600 patients (pts) with advanced Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol 12(11):S1793
Hendriks LEL et al (2019) Outcome of patients with non-small cell lung Cancer and brain metastases treated with checkpoint inhibitors. J Thorac Oncol 14:1244
Demaria S, Formenti SC (2012) Role of T lymphocytes in tumor response to radiotherapy. Front Oncol 2:95
Sharabi AB et al (2015) Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol 16(13):e498–e509
Demaria S, Golden EB, Formenti SC (2015) Role of local radiation therapy in cancer immunotherapy. JAMA Oncol 1(9):1325
Gupta A et al (2012) Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol 189(2):558–566
Herter-Sprie GS et al (2016) Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer. JCI Insight 1(9):e87415
Shaverdian N et al (2017) Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 18(7):895–903
Ahmed KA et al (2017) Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. J Neuro-Oncol 133(2):331–338
Williams NL et al (2017) Phase 1 study of Ipilimumab combined with whole brain radiation therapy or radiosurgery for melanoma patients with brain metastases. Int J Radiat Oncol Biol Phys 99(1):22–30
Anderson ES et al (2017) Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. J Immunother Cancer 5(1):76
Lehrer EJ et al (2018) Stereotactic radiosurgery and immune checkpoint inhibitors in the management of brain metastases. Int J Mol Sci 19(10):3054
Lehrer EJ et al (2019) Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: an international meta-analysis of individual patient data. Radiother Oncol 130:104–112
Schoenfeld JD et al (2015) Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review. J Immunother Cancer 3:50
Chen L et al (2018) Concurrent immune checkpoint inhibitors and stereotactic radiosurgery for brain metastases in non-small cell lung cancer, melanoma, and renal cell carcinoma. Int J Radiat Oncol Biol Phys 100(4):916–925
Colaco RJ et al (2016) Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? J Neurosurg 125(1):17–23
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Collier, E.F., Chiang, V., Goldberg, S.B. (2021). Management of Brain Metastases. In: Chiang, A.C., Herbst, R.S. (eds) Lung Cancer. Current Cancer Research. Humana, Cham. https://doi.org/10.1007/978-3-030-74028-3_6
Download citation
DOI: https://doi.org/10.1007/978-3-030-74028-3_6
Published:
Publisher Name: Humana, Cham
Print ISBN: 978-3-030-74027-6
Online ISBN: 978-3-030-74028-3
eBook Packages: MedicineMedicine (R0)