Management of brain metastases according to molecular subtypes.
Antineoplastic Agents
/ administration & dosage
Antineoplastic Agents, Immunological
/ administration & dosage
Brain Neoplasms
/ immunology
Breast Neoplasms
/ immunology
Combined Modality Therapy
/ methods
Disease Management
Drug Delivery Systems
/ methods
Female
Humans
Lung Neoplasms
/ immunology
Melanoma
/ immunology
Molecular Targeted Therapy
/ methods
Radiosurgery
/ methods
Journal
Nature reviews. Neurology
ISSN: 1759-4766
Titre abrégé: Nat Rev Neurol
Pays: England
ID NLM: 101500072
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
accepted:
14
07
2020
pubmed:
3
9
2020
medline:
18
1
2022
entrez:
3
9
2020
Statut:
ppublish
Résumé
The incidence of brain metastases has markedly increased in the past 20 years owing to progress in the treatment of malignant solid tumours, earlier diagnosis by MRI and an ageing population. Although local therapies remain the mainstay of treatment for many patients with brain metastases, a growing number of systemic options are now available and/or are under active investigation. HER2-targeted therapies (lapatinib, neratinib, tucatinib and trastuzumab emtansine), alone or in combination, yield a number of intracranial responses in patients with HER2-positive breast cancer brain metastases. New inhibitors are being investigated in brain metastases from ER-positive or triple-negative breast cancer. Several generations of EGFR and ALK inhibitors have shown activity on brain metastases from EGFR and ALK mutant non-small-cell lung cancer. Immune-checkpoint inhibitors (ICIs) hold promise in patients with non-small-cell lung cancer without druggable mutations and in patients with triple-negative breast cancer. The survival of patients with brain metastases from melanoma has substantially improved after the advent of BRAF inhibitors and ICIs (ipilimumab, nivolumab and pembrolizumab). The combination of targeted agents or ICIs with stereotactic radiosurgery could further improve the response rates and survival but the risk of radiation necrosis should be monitored. Advanced neuroimaging and liquid biopsy will hopefully improve response evaluation.
Identifiants
pubmed: 32873927
doi: 10.1038/s41582-020-0391-x
pii: 10.1038/s41582-020-0391-x
doi:
Substances chimiques
Antineoplastic Agents
0
Antineoplastic Agents, Immunological
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
557-574Références
Kromer, C. et al. Estimating the annual frequency of synchronous brain metastasis in the United States 2010-2013: a population-based study. J. Neurooncol. 134, 55–64 (2017).
pubmed: 28567587
doi: 10.1007/s11060-017-2516-7
Soffietti, R. et al. Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro Oncol. 19, 162–174 (2017).
pubmed: 28391295
pmcid: 5620494
doi: 10.1093/neuonc/now241
National Comprehensive Cancer Network. Central nervous system cancers: extensive brain metastases. v.4.2012. http://www.nccn.org (2019).
Brastianos, P. K. et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov. 5, 1164–1177 (2015).
pubmed: 26410082
pmcid: 4916970
doi: 10.1158/2159-8290.CD-15-0369
Shih, D. J. H. et al. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma. Nat. Genet. 52, 371–377 (2020).
pubmed: 32203465
pmcid: 7136154
doi: 10.1038/s41588-020-0592-7
Kim, M. et al. Barriers to effective drug treatment for brain metastases: a multifactorial problem in the delivery of precision medicine. Pharm. Res. 35, 177 (2018).
pubmed: 30003344
pmcid: 6700736
doi: 10.1007/s11095-018-2455-9
Sprowls, S. A. et al. Improving CNS delivery to brain metastases by blood-tumor barrier disruption. Trends Cancer 5, 495–505 (2019).
pubmed: 31421906
pmcid: 6703178
doi: 10.1016/j.trecan.2019.06.003
Lockman, P. R. et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin. Cancer Res. 16, 5664–5678 (2010).
pubmed: 20829328
pmcid: 2999649
doi: 10.1158/1078-0432.CCR-10-1564
Morikawa, A. et al. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro Oncol. 17, 289–295 (2015).
pubmed: 25015089
doi: 10.1093/neuonc/nou141
Pardridge, W. M. CSF, blood-brain barrier, and brain drug delivery. Expert. Opin. Drug Deliv. 13, 963–975 (2016).
pubmed: 27020469
doi: 10.1517/17425247.2016.1171315
Noone A. M. et al. SEER Cancer Statistics Review, 1975-2015. (National Cancer Institute, 2015).
Sørensen, J. B., Hansen, H. H., Hansen, M. & Dombernowsky, P. Brain metastases in adenocarcinoma of the lung: frequency, risk groups, and prognosis. J. Clin. Oncol. 6, 1474–1480 (1988).
pubmed: 3047337
doi: 10.1200/JCO.1988.6.9.1474
Sperduto, P. W. et al. Estimating survival in patients with lung cancer and brain metastases: an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-MolGPA). JAMA Oncol. 3, 827–831 (2017).
pubmed: 27892978
doi: 10.1001/jamaoncol.2016.3834
Kris, M. G. et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311, 1998–2006 (2014).
pubmed: 24846037
pmcid: 4163053
doi: 10.1001/jama.2014.3741
Dong, J., Li, B., Lin, D., Zhou, Q. & Huang, D. Advances in targeted therapy and immunotherapy for non-small cell lung cancer based on accurate molecular typing. Front. Pharmacol. 10, 230 (2019).
pubmed: 30930778
pmcid: 6424010
doi: 10.3389/fphar.2019.00230
Rosell, R. et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361, 958–967 (2009).
pubmed: 19692684
doi: 10.1056/NEJMoa0904554
Pao, W. et al. EGF receptor gene mutations are common in lung cancers from ‘Never Smokers’ and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc. Natl Acad. Sci. USA 101, 13306–13311 (2004).
pubmed: 15329413
doi: 10.1073/pnas.0405220101
pmcid: 516528
Eichler, A. F. et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol. 12, 1193–1199 (2010).
pubmed: 20627894
pmcid: 3098020
doi: 10.1093/neuonc/noq076
Wu, Y. L. 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). Ann. Oncol. 24, 993–999 (2013).
pubmed: 23129122
doi: 10.1093/annonc/mds529
Welsh, J. W. 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. Clin. Oncol. 31, 895–902 (2013).
pubmed: 23341526
pmcid: 3577951
doi: 10.1200/JCO.2011.40.1174
Iuchi, T. et al. Phase II trial of gefitinib alone without radiation therapy for japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma. Lung Cancer 82, 282–287 (2013).
pubmed: 24021541
doi: 10.1016/j.lungcan.2013.08.016
Yang, J. J. et al. Icotinib versus Whole-Brain Irradiation in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer and Multiple Brain Metastases (BRAIN): A Multicentre, Phase 3, Open-Label, Parallel, Randomised Controlled Trial. Lancet Respir. Med. 5, 707–716 (2017).
pubmed: 28734822
doi: 10.1016/S2213-2600(17)30262-X
Zhao, J. et al. Cerebrospinal fluid concentrations of gefitinib in patients with lung adenocarcinoma. Clin. Lung Cancer 14, 188–193 (2013).
pubmed: 22846582
doi: 10.1016/j.cllc.2012.06.004
Deng, Y. et al. The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer. Mol. Clin. Oncol. 2, 116–120 (2014).
pubmed: 24649318
doi: 10.3892/mco.2013.190
Grommes, C. et al. ‘Pulsatile’ high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol. 13, 1364–1369 (2011).
pubmed: 21865399
pmcid: 3223088
doi: 10.1093/neuonc/nor121
How, J., Mann, J., Laczniak, A. N. & Baggstrom, M. Q. Pulsatile erlotinib in EGFR-positive non-small-cell lung cancer patients with leptomeningeal and brain metastases: review of the literature. Clin. Lung Cancer 18, 354–363 (2017).
pubmed: 28245967
doi: 10.1016/j.cllc.2017.01.013
Yu, H. A. et al. 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, 278–284 (2017).
pubmed: 28073786
doi: 10.1093/annonc/mdw556
Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786–792 (2005).
pubmed: 15728811
doi: 10.1056/NEJMoa044238
Sequist, L. V. et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl Med. 3, 75ra26 (2011).
pubmed: 21430269
pmcid: 3132801
doi: 10.1126/scitranslmed.3002003
Camidge, D. R., Pao, W. & Sequist, L. V. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat. Rev. Clin. Oncol. 11, 473–481 (2014).
pubmed: 24981256
doi: 10.1038/nrclinonc.2014.104
Sequist, L. V. et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol. 31, 3327–3334 (2013).
pubmed: 23816960
doi: 10.1200/JCO.2012.44.2806
Wu, Y. L. et al. 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, 213–222 (2014).
pubmed: 24439929
doi: 10.1016/S1470-2045(13)70604-1
Herbst, R. S., Morgensztern, D. & Boshoff, C. The biology and management of non-small cell lung cancer. Nature 553, 446–454 (2018).
pubmed: 29364287
doi: 10.1038/nature25183
Jänne, P. A. et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N. Engl. J. Med. 372, 1689–1699 (2015).
pubmed: 25923549
doi: 10.1056/NEJMoa1411817
Soria, J. C. et al. Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer. N. Engl. J. Med. 378, 113–125 (2018).
pubmed: 29151359
doi: 10.1056/NEJMoa1713137
Reungwetwattana, T. et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J. Clin. Oncol. 36, 3290–3297 (2018).
doi: 10.1200/JCO.2018.78.3118
Ramalingam, S. S. et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med. 382, 41–50 (2020).
pubmed: 31751012
doi: 10.1056/NEJMoa1913662
Wu, Y. L. et al. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J. Clin. Oncol. 36, 2702–2709 (2018).
pubmed: 30059262
doi: 10.1200/JCO.2018.77.9363
Takeuchi, K. et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin. Cancer Res. 14, 6618–6624 (2008).
pubmed: 18927303
doi: 10.1158/1078-0432.CCR-08-1018
Wong, D. W. et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 115, 1723–1733 (2009).
pubmed: 19170230
doi: 10.1002/cncr.24181
Shaw, A. T. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med. 368, 2385–2394 (2013).
pubmed: 23724913
doi: 10.1056/NEJMoa1214886
Solomon, B. J. et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N. Engl. J. Med. 371, 2167–2177 (2014).
pubmed: 25470694
doi: 10.1056/NEJMoa1408440
Solomon, B. J. et al. 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, 2858–2865 (2016).
pubmed: 27022118
doi: 10.1200/JCO.2015.63.5888
Shaw, A. T. et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 17, 234–242 (2016).
pubmed: 26708155
doi: 10.1016/S1470-2045(15)00488-X
Kim, D. W. et al. 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, 2490–2498 (2017).
pubmed: 28475456
doi: 10.1200/JCO.2016.71.5904
Nishio, M. et al. Final overall survival and other efficacy and safety results from ASCEND-3: phase II study of ceritinib in ALKi-naive patients with ALK-rearranged NSCLC. J. Thorac. Oncol. 15, 609–617 (2020).
pubmed: 31778798
doi: 10.1016/j.jtho.2019.11.006
Gadgeel, S. M. et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 15, 1119–1128 (2014).
pubmed: 25153538
doi: 10.1016/S1470-2045(14)70362-6
Peters, S. et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N. Engl. J. Med. 377, 829–838 (2017).
pubmed: 28586279
doi: 10.1056/NEJMoa1704795
Solomon, B. J. et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 19, 1654–1667 (2018).
pubmed: 30413378
doi: 10.1016/S1470-2045(18)30649-1
Russo, A. et al. New targets in lung cancer (Excluding EGFR, ALK, ROS1). Curr. Oncol. Rep. 22, 48 (2020).
pubmed: 32296961
doi: 10.1007/s11912-020-00909-8
Planchard, D. et al. 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, 984–993 (2016).
pubmed: 27283860
pmcid: 4993103
doi: 10.1016/S1470-2045(16)30146-2
Drilon, A. et al. Activity of larotrectinib in TRK fusion lung cancer. Ann. Oncol. 30 (Suppl. 2), ii48–ii49 (2019).
doi: 10.1093/annonc/mdz063.009
Drilon, A. et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol. 21, 261–270 (2020).
pubmed: 31838015
doi: 10.1016/S1470-2045(19)30690-4
Scheel, A. H. et al. PDL-1 expression in non-small cell lung cancer: correlations with genetic alterations. Oncoimmunology 5, e1131379 (2016).
pubmed: 27467949
pmcid: 4910698
doi: 10.1080/2162402X.2015.1131379
Takamori, S. et al. Clinical significance of PDL-1 expression in brain metastases from non-small cell lung cancer. Anticancer Res. 38, 553–557 (2018).
pubmed: 29277823
Mansfield, A. S. et al. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Ann. Oncol. 27, 1953–1958 (2016).
pubmed: 27502709
pmcid: 5035793
doi: 10.1093/annonc/mdw289
Goldberg, S. B. et al. 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, 655–663 (2020).
pubmed: 32251621
pmcid: 7380514
doi: 10.1016/S1470-2045(20)30111-X
Davis, A. A. & Patel, V. G. The role of PDL-1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J. Immunother. Cancer 7, 278–285 (2019).
pubmed: 31655605
pmcid: 6815032
doi: 10.1186/s40425-019-0768-9
Gadgeel, S. M. et al. 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 (2019).
pubmed: 30642441
doi: 10.1016/j.lungcan.2018.12.017
Gong, X. et al. Combined radiotherapy and Anti-PDL-1 antibody synergistically enhances antitumor effect in non-small cell lung cancer. J. Thorac. Oncol. 12, 1085–1097 (2017).
pubmed: 28478231
doi: 10.1016/j.jtho.2017.04.014
Singh, C., Qian, J. M., Yu, J. B. & Chiang, V. L. Local tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non-small cell lung cancer with brain metastases. J. Neurosurg. 132, 512–517 (2019).
pubmed: 30771783
doi: 10.3171/2018.10.JNS181371
Chen, L. et al. 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, 916–925 (2018).
pubmed: 29485071
doi: 10.1016/j.ijrobp.2017.11.041
Kotecha, R. et al. The impact of sequencing PD-1/PDL-1 inhibitors and stereotactic radiosurgery for patients with brain metastasis. Neuro Oncol. 21, 1060–1068 (2019).
pmcid: 6682202
doi: 10.1093/neuonc/noz046
pubmed: 30796838
Lin, N. U. et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 118, 5463–5472 (2012).
pubmed: 22544643
doi: 10.1002/cncr.27581
Olson, E. M. et al. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab. Ann. Oncol. 24, 1526–1533 (2013).
pubmed: 23463626
pmcid: 3660080
doi: 10.1093/annonc/mdt036
Pestalozzi, B. C. et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol. 14, 244–248 (2013).
pubmed: 23414588
doi: 10.1016/S1470-2045(13)70017-2
Dawood, S. et al. Incidence of and survival following brain metastases among women with inflammatory breast cancer. Ann. Oncol. 21, 2348–2355 (2010).
pubmed: 20439340
doi: 10.1093/annonc/mdq239
Warren, L. E. et al. Inflammatory breast cancer and development of brain metastases: risk factors and outcomes. Breast Cancer Res. Treat. 151, 225–232 (2015).
pubmed: 25893587
doi: 10.1007/s10549-015-3381-8
Lin, N. U. et al. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer 113, 2638–2645 (2008).
pubmed: 18833576
doi: 10.1002/cncr.23930
Kennecke, H. et al. Metastatic behavior of breast cancer subtypes. J. Clin. Oncol. 28, 3271–3277 (2010).
pubmed: 20498394
doi: 10.1200/JCO.2009.25.9820
Ramakrishna, N. et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: ASCO clinical practice guideline update. J. Clin. Oncol. 36, 2804–2807 (2018).
pubmed: 29939840
doi: 10.1200/JCO.2018.79.2713
Olson, E. M. et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast 22, 525–531 (2013).
pubmed: 23352568
doi: 10.1016/j.breast.2012.12.006
von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N. Engl. J. Med. 380, 617–628 (2019).
doi: 10.1056/NEJMoa1814017
Bendell, J. C. et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97, 2972–2977 (2003).
pubmed: 12784331
doi: 10.1002/cncr.11436
Sperduto, P. W. 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. Clin. Oncol. 30, 419–425 (2012).
pubmed: 22203767
doi: 10.1200/JCO.2011.38.0527
Cagney, D. N. et al. Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases. Breast Cancer Res. Treat. 176, 171–179 (2019).
pubmed: 30982195
doi: 10.1007/s10549-019-05236-6
Gori, S. et al. The HERBA study: a retrospective multi-institutional Italian study on patients with brain metastases from HER2-positive breast cancer. Clin. Breast Cancer 19, e501–e510 (2019).
pubmed: 31204290
doi: 10.1016/j.clbc.2019.05.006
Palmieri, D. et al. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res. 67, 4190–4198 (2007).
pubmed: 17483330
doi: 10.1158/0008-5472.CAN-06-3316
Taskar, K. S. et al. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer. Pharm. Res. 29, 770–781 (2012).
pubmed: 22011930
doi: 10.1007/s11095-011-0601-8
Lin, N. U. et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J. Clin. Oncol. 26, 1993–1999 (2008).
pubmed: 18421051
doi: 10.1200/JCO.2007.12.3588
Lin, N. U. et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin. Cancer Res. 15, 1452–1459 (2009).
pubmed: 19228746
doi: 10.1158/1078-0432.CCR-08-1080
Sutherland, S. et al. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases–the UK experience. Br. J. Cancer 102, 995–1002 (2010).
pubmed: 20179708
pmcid: 2844035
doi: 10.1038/sj.bjc.6605586
Lin, N. U. et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J. Neurooncol. 105, 613–620 (2011).
pubmed: 21706359
doi: 10.1007/s11060-011-0629-y
Metro, G. et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann. Oncol. 22, 625–630 (2011).
pubmed: 20724575
doi: 10.1093/annonc/mdq434
Bachelot, T. et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 14, 64–71 (2013).
pubmed: 23122784
doi: 10.1016/S1470-2045(12)70432-1
Freedman, R. A. et al. Pre- and postoperative neratinib for HER2-positive breast cancer brain metastases: translational breast cancer research consortium 022. Clin. Breast Cancer 20, 145–151.e2 (2020).
pubmed: 31558424
doi: 10.1016/j.clbc.2019.07.011
Freedman, R. A. et al. Translational breast cancer research consortium (TBCRC) 022: A phase II trial of neratinib for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J. Clin. Oncol. 34, 945–952 (2016).
pubmed: 26834058
pmcid: 5070554
doi: 10.1200/JCO.2015.63.0343
Freedman, R. A. et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J. Clin. Oncol. 37, 1081–1089 (2019).
pubmed: 30860945
pmcid: 6494354
doi: 10.1200/JCO.18.01511
Metzger-Filho, O. et al. Phase I dose-escalation trial of ONT-380 in combination with trastuzumab in participants with brain metastases from HER2
Murthy, R. et al. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol. 19, 880–888 (2018).
pubmed: 29804905
doi: 10.1016/S1470-2045(18)30256-0
Murthy, R. K. et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N. Engl. J. Med. 382, 597–609 (2020).
pubmed: 31825569
doi: 10.1056/NEJMoa1914609
Dijkers, E. C. et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin. Pharmacol. Ther. 87, 586–592 (2010).
pubmed: 20357763
doi: 10.1038/clpt.2010.12
Lewis Phillips, G. D. et al. Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis. Breast Cancer Res. Treat. 164, 581–591 (2017).
pubmed: 28493046
pmcid: 5495871
doi: 10.1007/s10549-017-4279-4
Lin, N. U. et al. Planned interim analysis of PATRICIA: an open-label, single-arm, phase II study of pertuzumab (P) with high-dose trastuzumab (H) for the treatment of central nervous system (CNS) progression post radiotherapy (RT) in patients (pts) with HER2-positive metastatic breast cancer (MBC). J. Clin. Oncol. 35 (Suppl. 15), 2074 (2017).
doi: 10.1200/JCO.2017.35.15_suppl.2074
Bartsch, R. et al. Activity of T-DM1 in Her2-positive breast cancer brain metastases. Clin. Exp. Metastasis 32, 729–737 (2015).
pubmed: 26303828
doi: 10.1007/s10585-015-9740-3
Jacot, W. et al. Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res. Treat. 157, 307–318 (2016).
pubmed: 27167986
doi: 10.1007/s10549-016-3828-6
Askoxylakis, V., Kodack, D. P., Ferraro, G. B. & Jain, R. K. Antibody-based therapies for the treatment of brain metastases from HER2-positive breast cancer: time to rethink the importance of the BBB? Breast Cancer Res. Treat. 165, 467–468 (2017).
pubmed: 28643019
doi: 10.1007/s10549-017-4351-0
Fabi, A. et al. T-DM1 and brain metastases: clinical outcome in HER2-positive metastatic breast cancer. Breast 41, 137–143 (2018).
pubmed: 30092500
doi: 10.1016/j.breast.2018.07.004
Modi, S. et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N. Engl. J. Med. 382, 610–621 (2020).
pubmed: 31825192
doi: 10.1056/NEJMoa1914510
Lin, N. U., Bellon, J. R. & Winer, E. P. CNS metastases in breast cancer. J. Clin. Oncol. 22, 3608–3617 (2004).
pubmed: 15337811
doi: 10.1200/JCO.2004.01.175
Raub, T. J. et al. Brain exposure of two selective dual CDK4 and CDK6 inhibitors and the antitumor activity of CDK4 and CDK6 inhibition in combination with temozolomide in an intracranial glioblastoma xenograft. Drug Metab. Dispos. 43, 1360–1371 (2015).
pubmed: 26149830
doi: 10.1124/dmd.114.062745
Anders, C. K. et al. A phase 2 study of abemaciclib in patients (pts) with brain metastases (BM) secondary to HR
doi: 10.1200/JCO.2019.37.15_suppl.1017
Patel, H. K. & Bihani, T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacol. Ther. 186, 1–24 (2018).
pubmed: 29289555
doi: 10.1016/j.pharmthera.2017.12.012
Ni, J. et al. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat. Med. 22, 723–726 (2016).
pubmed: 27270588
pmcid: 4938731
doi: 10.1038/nm.4120
Kodack, D. P. et al. The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation. Sci. Transl Med. 9, 391 (2017).
doi: 10.1126/scitranslmed.aal4682
Ippen, F. M. et al. Targeting the PI3K/Akt/mTOR-pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases. Neuro Oncol. 21, 1401–1411 (2019).
pubmed: 31173106
doi: 10.1093/neuonc/noz105
pmcid: 6827829
Song, Y. et al. Patterns of recurrence and metastasis in BRCA1/BRCA2-associated breast cancers. Cancer 126, 271–280 (2020).
pubmed: 31581314
doi: 10.1002/cncr.32540
Puri, A., Reddy, T. P., Patel, T. A. & Chang, J. C. Metastatic triple-negative breast cancer: established and emerging treatments. Breast J. https://doi.org/10.1111/tbj.13946 (2020).
Litton, J. K. et al. Neoadjuvant talazoparib for patients with operable breast cancer with a germline BRCA pathogenic variant. J. Clin. Oncol. 38, 388–394 (2020).
pubmed: 31461380
doi: 10.1200/JCO.19.01304
Karginova, O. et al. Efficacy of carboplatin alone and in combination with ABT888 in intracranial murine models of BRCA-mutated and BRCA-wild-type triple-negative breast cancer. Mol. Cancer Ther. 14, 920–930 (2015).
pubmed: 25824335
pmcid: 4394032
doi: 10.1158/1535-7163.MCT-14-0474
Voutouri, C. et al. Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies. Proc. Natl Acad. Sci. USA 116, 2662–2671 (2019).
pubmed: 30700544
doi: 10.1073/pnas.1818322116
pmcid: 6377457
Kodack, D. P. et al. Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. Proc. Natl Acad. Sci. USA 109, E3119–E3127 (2012).
pubmed: 23071298
doi: 10.1073/pnas.1216078109
pmcid: 3494882
Lin, N. U. et al. Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM). J. Clin. Oncol. 31 (Suppl. 15), 513 (2013).
doi: 10.1200/jco.2013.31.15_suppl.513
Lu, Y. S. et al. Bevacizumab preconditioning followed by etoposide and cisplatin is highly effective in treating brain metastases of breast cancer progressing from whole-brain radiotherapy. Clin. Cancer Res. 21, 1851–1858 (2015).
pubmed: 25700303
doi: 10.1158/1078-0432.CCR-14-2075
Wagner, A. D., Thomssen, C., Haerting, J. & Unverzagt, S. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst. Rev. 7, CD008941 (2012).
Schmid, P. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21, 44–59 (2020).
pubmed: 31786121
doi: 10.1016/S1470-2045(19)30689-8
Duchnowska, R. et al. Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis. Breast Cancer Res. 18, 43 (2016).
pubmed: 27117582
pmcid: 4847231
doi: 10.1186/s13058-016-0702-8
Ogiya, R. et al. Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer. Oncotarget 8, 103671–103681 (2017).
pubmed: 29262592
pmcid: 5732758
doi: 10.18632/oncotarget.22110
Yomo, S., Hayashi, M. & Cho, N. Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer. J. Neurooncol. 112, 199–207 (2013).
pubmed: 23296546
doi: 10.1007/s11060-013-1046-1
Kim, J. M. et al. Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis. Neuro Oncol. 21, 659–668 (2019).
pubmed: 30726965
pmcid: 6502492
doi: 10.1093/neuonc/noz006
Parsai, S. et al. Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases. J. Neurosurg. 132, 503–511 (2019).
pubmed: 30738402
doi: 10.3171/2018.10.JNS182340
Lin, N. U. et al. A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases. Breast Cancer Res. Treat. 142, 405–414 (2013).
pubmed: 24197661
doi: 10.1007/s10549-013-2754-0
Stumpf, P. K. et al. Combination of trastuzumab emtansine and stereotactic radiosurgery results in high rates of clinically significant radionecrosis and dysregulation of aquaporin-4. Clin. Cancer Res. 25, 3946–3953 (2019).
pubmed: 30940654
pmcid: 6751332
doi: 10.1158/1078-0432.CCR-18-2851
Geraud, A., Xu, H. P., Beuzeboc, P. & Kirova, Y. M. Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer. J. Neurooncol. 131, 69–72 (2017).
pubmed: 27995546
doi: 10.1007/s11060-016-2265-z
Rosner, D., Nemoto, T. & Lane, W. W. Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer 58, 832–839 (1986).
pubmed: 3755076
doi: 10.1002/1097-0142(19860815)58:4<832::AID-CNCR2820580404>3.0.CO;2-W
Franciosi, V. et al. Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: a prospective study. Cancer 85, 1599–1605 (1999).
pubmed: 10193952
doi: 10.1002/(SICI)1097-0142(19990401)85:7<1599::AID-CNCR23>3.0.CO;2-#
Christodoulou, C. et al. Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) phase II study. J. Neurooncol. 71, 61–65 (2005).
pubmed: 15719277
doi: 10.1007/s11060-004-9176-0
Caraglia, M. et al. Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. Cancer Chemother. Pharmacol. 57, 34–39 (2006).
pubmed: 16010592
doi: 10.1007/s00280-005-0001-z
Rivera, E. et al. Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Cancer 107, 1348–1354 (2006).
pubmed: 16909414
doi: 10.1002/cncr.22127
Linot, B. et al. Use of liposomal doxorubicin-cyclophosphamide combination in breast cancer patients with brain metastases: a monocentric retrospective study. J. Neurooncol. 117, 253–259 (2014).
pubmed: 24481998
doi: 10.1007/s11060-014-1378-5
Anders, C. et al. TBCRC 018: phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Breast Cancer Res. Treat. 146, 557–566 (2014).
pubmed: 25001612
pmcid: 4112043
doi: 10.1007/s10549-014-3039-y
Melisko, M. E. et al. Phase II study of irinotecan and temozolomide in breast cancer patients with progressing central nervous system disease. Breast Cancer Res. Treat. 177, 401–408 (2019).
pubmed: 31172405
doi: 10.1007/s10549-019-05309-6
Shah, N. et al. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. Pharmacol. Res. 132, 47–68 (2018).
pubmed: 29604436
pmcid: 5997530
doi: 10.1016/j.phrs.2018.03.021
Cortés, J. et al. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res. Treat. 165, 329–341 (2017).
pubmed: 28612225
pmcid: 5543189
doi: 10.1007/s10549-017-4304-7
Anders, C. et al. Phase 1 expansion study of irinotecan liposome injection (nal-IRI) in patients with metastatic breast cancer (mBC): findings from the cohort with active brain metastasis (BM). Neuro-oncol. Adv. 1 (Suppl. 1), https://doi.org/10.1093/noajnl/vdz014.039 (2019).
Kumthekar, P. et al. ANG1005, a novel brain-penetrant taxane derivative, for the treatment of recurrent brain metastases and leptomeningeal carcinomatosis from breast cancer. J. Clin. Oncol. 34 (Suppl. 15), 2004 (2016).
doi: 10.1200/JCO.2016.34.15_suppl.2004
James, J., Tang, K. & Wei, T. Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier (BBB) at therapeutically relevant concentrations [abstract 3078]. Cancer Res. 79 (Suppl. 13), https://doi.org/10.1158/1538-7445.AM2019-3078 (2019).
Seidman, A. D. et al. Activity of tesetaxel, an oral taxane, given as a single-agent in patients (Pts) with HER2
Zakrzewski, J. et al. Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastases and post-brain metastases survival. Cancer 117, 1711–1720 (2011).
pubmed: 21472718
doi: 10.1002/cncr.25643
Jakob, J. A. et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 118, 4014–4023 (2012).
pubmed: 22180178
doi: 10.1002/cncr.26724
Bucheit, A. D. et al. Clinical characteristics and outcomes with specific BRAF and NRAS mutations in patients with metastatic melanoma. Cancer 119, 3821–3829 (2013).
pubmed: 23922205
doi: 10.1002/cncr.28306
Hanniford, D. et al. A miRNA-based signature detected in primary melanoma tissue predicts development of brain metastasis. Clin. Cancer Res. 21, 4903–4912 (2015).
pubmed: 26089374
pmcid: 4631639
doi: 10.1158/1078-0432.CCR-14-2566
Fischer, G. M. et al. Molecular profiling reveals unique immune and metabolic features of melanoma brain metastases. Cancer Discov. 9, 628–645 (2019).
pubmed: 30787016
pmcid: 6497554
doi: 10.1158/2159-8290.CD-18-1489
Davies, M. A. et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer 117, 1687–1696 (2011).
pubmed: 20960525
doi: 10.1002/cncr.25634
Sperduto, P. W. et al. Estimating survival in melanoma patients with brain metastases: an update of the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA). Int. J. Radiat. Oncol. Biol. Phys. 99, 812–816 (2017).
pubmed: 29063850
pmcid: 6925529
doi: 10.1016/j.ijrobp.2017.06.2454
Sloot, S. et al. Improved survival of patients with melanoma brain metastases in the era of targeted BRAF and immune checkpoint therapies. Cancer 124, 297–305 (2018).
pubmed: 29023643
doi: 10.1002/cncr.30946
Iorgulescu, J. B. et al. Improved risk-adjusted survival for melanoma brain metastases in the era of checkpoint blockade immunotherapies: results from a national cohort. Cancer Immunol. Res. 6, 1039–1045 (2018).
pubmed: 30002157
pmcid: 6230261
doi: 10.1158/2326-6066.CIR-18-0067
Schvartsman, G. et al. Incidence, patterns of progression and outcomes of preexisting and newly discovered brain metastases during treatment with anti-PD-1 in patients with metastatic melanoma. Cancer 125, 4193–4202 (2019).
pubmed: 31398264
doi: 10.1002/cncr.32454
Colombino, M. et al. BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. J. Clin. Oncol. 30, 2522–2529 (2012).
pubmed: 22614978
doi: 10.1200/JCO.2011.41.2452
Chapman, P. B. et al. BRIM-3 study group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507–2516 (2011).
pubmed: 21639808
pmcid: 3549296
doi: 10.1056/NEJMoa1103782
Dummer, R. et al. Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur. J. Cancer 50, 611–621 (2014).
pubmed: 24295639
doi: 10.1016/j.ejca.2013.11.002
McArthur, G. A. et al. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann. Oncol. 28, 634–641 (2017).
pubmed: 27993793
doi: 10.1093/annonc/mdw641
Long, G. V. et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 13, 1087–1095 (2012).
pubmed: 23051966
doi: 10.1016/S1470-2045(12)70431-X
Mittapalli, R. K., Vaidhyanathan, S., Dudek, A. Z. & Elmquist, W. F. Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J. Pharmacol. Exp. Ther. 344, 655–664 (2013).
pubmed: 23249624
pmcid: 3583506
doi: 10.1124/jpet.112.201475
Davies, M. A. et al. Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 18, 863–873 (2017).
pubmed: 28592387
pmcid: 5991615
doi: 10.1016/S1470-2045(17)30429-1
Vaidhyanathan, S., Mittapalli, R. K., Sarkaria, J. N. & Elmquist, W. F. Factors influencing the CNS distribution of a novel MEK-1/2 inhibitor: implications for combination therapy for melanoma brain metastases. Drug Metab. Dispos. 42, 1292–1300 (2014).
pubmed: 24875464
pmcid: 4109207
doi: 10.1124/dmd.114.058339
Drago, J. Z. et al. Clinical experience with combination BRAF/MEK inhibitors for melanoma with brain metastases: a real-life multicenter study. Melanoma Res. 29, 65–69 (2019).
pubmed: 30376465
doi: 10.1097/CMR.0000000000000527
Babiker, H. M. et al. E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases. Invest. N. Drugs 37, 636–645 (2019).
doi: 10.1007/s10637-018-0668-8
Niessner, H. et al. Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases. Cancer Med. 2, 76–85 (2013).
pubmed: 24133630
pmcid: 3797558
doi: 10.1002/cam4.50
Chen, G. et al. Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target. Clin. Cancer Res. 20, 5537–5546 (2014).
pubmed: 24803579
pmcid: 4216765
doi: 10.1158/1078-0432.CCR-13-3003
Gopal, Y. N. et al. Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and oxidative phosphorylation in melanoma. Cancer Res. 74, 7037–7047 (2014).
pubmed: 25297634
pmcid: 4347853
doi: 10.1158/0008-5472.CAN-14-1392
Tolcher, A. W. et al. A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors. Ann. Oncol. 26, 58–64 (2015).
pubmed: 25344362
doi: 10.1093/annonc/mdu482
Haueis, S. A. et al. Does the distribution pattern of brain metastases during BRAF inhibitor therapy reflect phenotype switching? Melanoma Res. 27, 231–237 (2017).
pubmed: 28099366
doi: 10.1097/CMR.0000000000000338
Margolin, K. et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 13, 459–465 (2012).
pubmed: 22456429
doi: 10.1016/S1470-2045(12)70090-6
Di Giacomo, A. M. et al. Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. Ann. Oncol. 26, 798–803 (2015).
pubmed: 25538176
doi: 10.1093/annonc/mdu577
Kluger, H. M. et al. Long-term survival of patients with melanoma with active brain metastases treated with pembrolizumab on a phase II trial. J. Clin. Oncol. 37, 52–60 (2019).
pubmed: 30407895
doi: 10.1200/JCO.18.00204
Tawbi, H. A. et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N. Engl. J. Med. 379, 722–730 (2018).
pubmed: 30134131
doi: 10.1056/NEJMoa1805453
pmcid: 8011001
Tawbi, H. A. et al. Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (CheckMate 204). J. Clin. Oncol. 37 (Suppl. 15), 9501 (2019).
doi: 10.1200/JCO.2019.37.15_suppl.9501
Long, G. V. et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 19, 672–681 (2018).
pubmed: 29602646
doi: 10.1016/S1470-2045(18)30139-6
Long, G. V. et al. Long-term outcomes from the randomized phase II study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets): anti-PD1 brain collaboration (ABC). Ann. Oncol. 30, v533–v563 (2019).
doi: 10.1093/annonc/mdz221
Cooper, Z. A. et al. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol. Res. 2, 643–654 (2014).
pubmed: 24903021
pmcid: 4097121
doi: 10.1158/2326-6066.CIR-13-0215
Frederick, D. T. et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin. Cancer Res. 19, 1225–1231 (2013).
pubmed: 23307859
pmcid: 3752683
doi: 10.1158/1078-0432.CCR-12-1630
Taggart, D. et al. Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8
pubmed: 29386395
doi: 10.1073/pnas.1714089115
pmcid: 5816160
Harter, P. N. et al. Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PDL-1 immune checkpoints in human brain metastases. Oncotarget 6, 40836–40849 (2015).
pubmed: 26517811
pmcid: 4747372
doi: 10.18632/oncotarget.5696
Cohen, J. V. et al. Melanoma brain metastasis pseudoprogression after pembrolizumab treatment. Cancer Immunol. Res. 4, 179–182 (2016).
pubmed: 26701266
doi: 10.1158/2326-6066.CIR-15-0160
Yi, M. et al. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment. Mol. Cancer 18, 60–64 (2019).
pubmed: 30925919
pmcid: 6441150
doi: 10.1186/s12943-019-0974-6
Manon, R. et al. Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J. Clin. Oncol. 23, 8870–8876 (2005).
pubmed: 16314647
doi: 10.1200/JCO.2005.01.8747
Sambade, M. J. et al. Melanoma cells show a heterogeneous range of sensitivity to ionizing radiation and are radiosensitized by inhibition of B-RAF with PLX-4032. Radiother. Oncol. 98, 394–399 (2011).
pubmed: 21295875
pmcid: 3050997
doi: 10.1016/j.radonc.2010.12.017
Narayana, A. et al. Vemurafenib and radiation therapy in melanoma brain metastases. J. Neurooncol. 113, 411–416 (2013).
pubmed: 23579338
doi: 10.1007/s11060-013-1127-1
Wolf, A. et al. Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases. J. Neurooncol. 127, 607–615 (2016).
pubmed: 26852222
doi: 10.1007/s11060-016-2072-6
Xu, Z. et al. BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases. J. Neurosurg. 126, 726–734 (2017).
pubmed: 27203149
doi: 10.3171/2016.2.JNS1633
Kotecha, R. et al. Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome. J. Neurosurg. 29, 50–59 (2018).
doi: 10.3171/2017.1.JNS162797
Mastorakos, P. et al. BRAF V600 mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases: a multicenter retrospective study. Neurosurgery 84, 868–880 (2019).
pubmed: 29846702
doi: 10.1093/neuros/nyy203
Lukas, R. V. Commentary: BRAF V600 mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases: a multicenter retrospective study. Neurosurgery 84, 881–882 (2019).
pubmed: 29846721
doi: 10.1093/neuros/nyy241
Anker, C. J. et al. Avoiding severe toxicity from combined BRAF inhibitor and radiation treatment: consensus guidelines from the eastern cooperative oncology group (ECOG). Int. J. Radiat. Oncol. Biol. Phys. 95, 632–646 (2016).
pubmed: 27131079
pmcid: 5102246
doi: 10.1016/j.ijrobp.2016.01.038
Patel, K. R. et al. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res. 26, 387–394 (2016).
pubmed: 27223498
pmcid: 4943024
doi: 10.1097/CMR.0000000000000268
Ly, D. et al. Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment. J. Neurosurg. 123, 395–401 (2015).
pubmed: 25768829
doi: 10.3171/2014.9.JNS141425
Walle, T. et al. Radiation effects on antitumor immune responses: current perspectives and challenges. Ther. Adv. Med. Oncol. 10, 1758834017742575 (2018).
pubmed: 29383033
pmcid: 5784573
doi: 10.1177/1758834017742575
Dewan, M. Z. et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin. Cancer Res. 15, 5379–5388 (2009).
pubmed: 19706802
pmcid: 2746048
doi: 10.1158/1078-0432.CCR-09-0265
Pfannenstiel, L. W. et al. Combination PD-1 blockade and irradiation of brain metastasis induces an effective abscopal effect in melanoma. Oncoimmunology 8, e1507669 (2018).
pubmed: 30546944
pmcid: 6287893
doi: 10.1080/2162402X.2018.1507669
Knisely, J. P. et al. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J. Neurosurg. 117, 227–233 (2012).
pubmed: 22702482
pmcid: 6098938
doi: 10.3171/2012.5.JNS111929
Silk, A. W., Bassetti, M. F., West, B. T., Tsien, C. I. & Lao, C. D. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2, 899–906 (2013).
pubmed: 24403263
pmcid: 3892394
doi: 10.1002/cam4.140
Kiess, A. P. et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int. J. Radiat. Oncol. Biol. Phys. 92, 368–375 (2015).
pubmed: 25754629
pmcid: 4955924
doi: 10.1016/j.ijrobp.2015.01.004
Sumimoto, H. et al. Effective inhibition of cell growth and invasion of melanoma by combined suppression of BRAF (V599E) and Skp2 with lentiviral RNAi. Int. J. Cancer 118, 472–476 (2006).
pubmed: 16052531
doi: 10.1002/ijc.21286
Colaco, R. J., Martin, P., Kluger, H. M., Yu, J. B. & Chiang, V. L. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? J. Neurosurg. 125, 17–23 (2016).
pubmed: 26544782
doi: 10.3171/2015.6.JNS142763
Patel, K. R. et al. Ipilimumab and stereotactic radiosurgery versus stereotactic radiosurgery alone for newly diagnosed melanoma brain metastases. Am. J. Clin. Oncol. 40, 444–450 (2017).
pubmed: 26017484
doi: 10.1097/COC.0000000000000199
Cohen-Inbar, O., Shih, H. H., Xu, Z., Schlesinger, D. & Sheehan, J. P. The effect of timing of stereotactic radiosurgery treatment of melanoma brain metastases treated with ipilimumab. J. Neurosurg. 127, 1007–1014 (2017).
pubmed: 28059663
doi: 10.3171/2016.9.JNS161585
Pin, Y. et al. Brain metastasis formation and irradiation by stereotactic radiation therapycombined with immunotherapy: a systematic review. Crit. Rev. Oncol. Hematol. 149, 102923 (2020).
pubmed: 32199131
doi: 10.1016/j.critrevonc.2020.102923
Forst, D. A. & Wen, P. Y. Neurological complications of targeted therapies in cancer neurology in clinical practice (eds D. Schiff, I. Arrillaga, P. Y. Wen) 311–334 (Springer, 2018).
Tran, T. T. et al. Complications associated with immunotherapy for brain metastases. Curr. Opin. Neurol. 32, 907–916 (2019).
pubmed: 31577604
pmcid: 7398556
doi: 10.1097/WCO.0000000000000756
Galldiks, N. et al. Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression. Neuro Oncol. 22, 17–30 (2019).
doi: 10.1093/neuonc/noz147
pmcid: 6954406
Hendriks, L. E. L. et al. Outcome of patients with non-small cell lung cancer and brain metastases treated with checkpoint inhibitors. J. Thorac. Oncol. 14, 1244–1254 (2019).
pubmed: 30780002
doi: 10.1016/j.jtho.2019.02.009
Rahman, R. et al. The impact of timing of immunotherapy with cranial irradiation in melanoma patients with brain metastases: intracranial progression, survival and toxicity. J. Neurooncol. 138, 299–306 (2018).
pubmed: 29453679
doi: 10.1007/s11060-018-2795-7
Okada, H. et al. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 16, 534–542 (2015).
doi: 10.1016/S1470-2045(15)00088-1
Champiat, S. et al. Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat. Rev. Clin. Oncol. 15, 748–762 (2018).
pubmed: 30361681
doi: 10.1038/s41571-018-0111-2
Ferrara, R. et al. Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with PD-1/PDL-1 inhibitors or with single-agent chemotherapy. JAMA Oncol. 4, 1543–1552 (2018).
pubmed: 30193240
pmcid: 6248085
doi: 10.1001/jamaoncol.2018.3676
Kanai, O., Fujita, K., Okamura, M., Nakatani, K. & Mio, T. Severe exacerbation or manifestation of primary disease related to nivolumab in non-small-cell lung cancer patients with poor performance status or brain metastases. Ann. Oncol. 27, 1354–1356 (2016).
pubmed: 27037297
doi: 10.1093/annonc/mdw148
Chuang, M. T., Liu, Y. S., Tsai, Y. S., Chen, Y. C. & Wang, C. K. Differentiating radiation-induced necrosis from recurrent brain tumor using MR perfusion and spectroscopy: a meta-analysis. PLoS ONE 11, e0141438 (2016).
pubmed: 26741961
pmcid: 4712150
doi: 10.1371/journal.pone.0141438
Galldiks, N. et al. PET imaging in patients with brain metastasis-report of the RANO/PET group. Neuro Oncol. 21, 585–595 (2019).
pubmed: 30615138
pmcid: 6502495
doi: 10.1093/neuonc/noz003
Abdulla, D. S. Y. et al. Monitoring treatment response to erlotinib in EGFR-mutated non-small-cell lung cancer brain metastases using serial O-(2-[
pubmed: 30528316
doi: 10.1016/j.cllc.2018.10.011
Kebir, S. et al. Dynamic O-(2-[
pubmed: 27591333
pmcid: 5035529
doi: 10.1093/neuonc/now154
Lohmann, P. et al. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase
pubmed: 27853813
doi: 10.1007/s00330-016-4638-2
Lohmann, P. et al. Combined FET PET/MRI radiomics differentiates radiation injury from recurrent brain metastasis. Neuroimage Clin. 20, 537–542 (2018).
pubmed: 30175040
pmcid: 6118093
doi: 10.1016/j.nicl.2018.08.024
Lin, N. U. et al. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 16, e270–e278 (2015).
pubmed: 26065612
doi: 10.1016/S1470-2045(15)70057-4
Camidge, D. R. et al. Clinical trial design for systemic agents in patients with brain metastases from solid tumours: a guideline by the response assessment in neuro-oncology brain metastases working group. Lancet Oncol. 19, e20–e32 (2018).
pubmed: 29304358
doi: 10.1016/S1470-2045(17)30693-9
Vogelbaum, M. A. et al. Phase 0 and window of opportunity clinical trial design in neuro-oncology: a RANO review. Neuro Oncol. https://doi.org/10.1093/neuonc/noaa149 (2020).
Boire, A. et al. Liquid biopsy in central nervous system metastases: a RANO review and proposals for clinical applications. Neuro Oncol. 21, 571–584 (2019).
pubmed: 30668804
pmcid: 6502489
doi: 10.1093/neuonc/noz012
Priego, N. et al. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat. Med. 24, 1024–1035 (2018).
pubmed: 29892069
doi: 10.1038/s41591-018-0044-4
Izraely, S. et al. The metastatic microenvironment: Melanoma-microglia cross-talk promotes the malignant phenotype of melanoma cells. Int. J. Cancer 144, 802–817 (2019).
pubmed: 29992556
doi: 10.1002/ijc.31745
Zeng, Q. et al. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature 573, 526–531 (2019).
pubmed: 31534217
pmcid: 6837873
doi: 10.1038/s41586-019-1576-6
Soffietti, R., Pellerino, A. & Rudà, R. Strategies to prevent brain metastasis. Curr. Opin. Oncol. 31, 493–500 (2019).
pubmed: 31414987
doi: 10.1097/CCO.0000000000000572