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Semin Neurol 2023; 43(06): 845-858
DOI: 10.1055/s-0043-1776782
Review Article

Management of Brain Metastases: A Review of Novel Therapies

Shreyas Bellur
1   Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
,
Atulya Aman Khosla
1   Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
,
Ahmad Ozair 
1   Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
3   Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
,
Rupesh Kotecha
1   Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
2   Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
,
Michael W. McDermott
2   Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
4   Miami Neuroscience Institute, Baptist Health South Florida, Miami, Florida
,
Manmeet S. Ahluwalia
1   Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
2   Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
› Author Affiliations Funding None.
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Abstract

Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery. The next generation of local strategies includes laser interstitial thermal therapy, magnetic hyperthermic therapy, post-resection brachytherapy, and focused ultrasound. New targeted therapies and immunotherapies with documented intracranial activity have transformed clinical outcomes. Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective “rearranged during transfection” inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody–drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.

Keywords

brain metastases - precision oncology - novel therapies - future directions - EGFR

Author Contributions

S.B: Conceptualization, methodology, original draft preparation, revising the manuscript, submission. A.A.K: Conceptualization, methodology, original draft preparation, revising the manuscript. A.O: Conceptualization, methodology, original draft preparation, revising the manuscript. R.K: Conceptualization, revising the manuscript. M.W.McD: Conceptualization, revising the manuscript. M.S.A: Conceptualization, revising the manuscript, supervision.




Publication History

Article published online:
27 November 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Ostrom QT, Price M, Neff C. et al. CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro-oncol 2022; 24 (Suppl. 05) v1-v95
    CrossrefPubMedSearch in Google Scholar
  • 2 Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004; 22 (14) 2865-2872
    CrossrefPubMedSearch in Google Scholar
  • 3 Sperduto PW, Mesko S, Li J. et al. Survival in patients with brain metastases: summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient. J Clin Oncol 2020; 38 (32) 3773-3784
    CrossrefPubMedSearch in Google Scholar
  • 4 Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer 2020; 20 (01) 26-41
    CrossrefPubMedSearch in Google Scholar
  • 5 Sperduto PW, Yang TJ, Beal K. 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 2017; 3 (06) 827-831
    CrossrefPubMedSearch in Google Scholar
  • 6 Sperduto PW, Jiang W, Brown PD. 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 2017; 99 (04) 812-816
    CrossrefPubMedSearch in Google Scholar
  • 7 Sperduto PW, Deegan BJ, Li J. et al. Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool. Neuro-oncol 2018; 20 (12) 1652-1660
    CrossrefPubMedSearch in Google Scholar
  • 8 Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 2008; 70 (02) 510-514
    CrossrefPubMedSearch in Google Scholar
  • 9 Le Rhun E, Weller M, Brandsma D. et al; EANO Executive Board and ESMO Guidelines Committee. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol 2017; 28 (Suppl. 04) iv84-iv99
    CrossrefPubMedSearch in Google Scholar
  • 10 Lote K, Stenwig AE, Skullerud K, Hirschberg H. Prevalence and prognostic significance of epilepsy in patients with gliomas. Eur J Cancer 1998; 34 (01) 98-102
    CrossrefPubMedSearch in Google Scholar
  • 11 van der Meer PB, Maschio M, Dirven L, Taphoorn MJB, Koekkoek JAF. Italian League Against Epilepsy Brain Tumor-Related Epilepsy Study Group. First-line levetiracetam versus enzyme-inducing antiseizure medication in glioma patients with epilepsy. Epilepsia 2023; 64 (01) 162-169
    CrossrefPubMedSearch in Google Scholar
  • 12 Chang SM, Messersmith H, Ahluwalia M. et al. Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: ASCO and SNO endorsement of the Congress of Neurological Surgeons Guidelines. J Clin Oncol 2019; 37 (13) 1130-1135
    CrossrefPubMedSearch in Google Scholar
  • 13 Patel TR, Knisely JP, Chiang VL. Management of brain metastases: surgery, radiation, or both?. Hematol Oncol Clin North Am 2012; 26 (04) 933-947
    CrossrefPubMedSearch in Google Scholar
  • 14 Prabhu RS, Kandula S, Liebman L. et al. Association of clinical response and long-term outcome among patients with biopsied orbital pseudotumor receiving modern radiation therapy. Int J Radiat Oncol Biol Phys 2013; 85 (03) 643-649
    CrossrefPubMedSearch in Google Scholar
  • 15 Vogelbaum MA, Brown PD, Messersmith H. et al. Treatment for brain metastases: ASCO-SNO-ASTRO Guideline. J Clin Oncol 2022; 40 (05) 492-516
    CrossrefPubMedSearch in Google Scholar
  • 16 Patchell RA, Tibbs PA, Walsh JW. et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990; 322 (08) 494-500
    CrossrefPubMedSearch in Google Scholar
  • 17 Patchell RA, Tibbs PA, Regine WF. et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998; 280 (17) 1485-1489
    CrossrefPubMedSearch in Google Scholar
  • 18 Chin AL, Li G, Gephart MH. et al. Stereotactic radiosurgery after resection of brain metastases: changing patterns of care in the United States. World Neurosurg 2020; 144: e797-e806
    CrossrefPubMedSearch in Google Scholar
  • 19 Mahajan A, Ahmed S, McAleer MF. et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18 (08) 1040-1048
    CrossrefPubMedSearch in Google Scholar
  • 20 Brown PD, Ballman KV, Cerhan JH. et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18 (08) 1049-1060
    CrossrefPubMedSearch in Google Scholar
  • 21 Palmer JD, Klamer BG, Ballman KV. et al. Association of long-term outcomes with stereotactic radiosurgery vs whole-brain radiotherapy for resected brain metastasis: a secondary analysis of the N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group) Randomized Clinical Trial. JAMA Oncol 2022; 8 (12) 1809-1815
    CrossrefPubMedSearch in Google Scholar
  • 22 Fuentes R, Osorio D, Expósito Hernandez J, Simancas-Racines D, Martinez-Zapata MJ, Bonfill Cosp X. Surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis. Cochrane Database Syst Rev 2018; 8 (08) CD012086
    PubMedSearch in Google Scholar
  • 23 Andrews DW, Scott CB, Sperduto PW. et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 2004; 363 (9422) 1665-1672
    CrossrefPubMedSearch in Google Scholar
  • 24 Gondi V, Bauman G, Bradfield L. et al. Radiation therapy for brain metastases: an ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2022; 12 (04) 265-282
    CrossrefPubMedSearch in Google Scholar
  • 25 Yamamoto M, Serizawa T, Shuto T. et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 2014; 15 (04) 387-395
    CrossrefPubMedSearch in Google Scholar
  • 26 Yamamoto M, Serizawa T, Sato Y, Higuchi Y, Kasuya H. Stereotactic radiosurgery results for patients with 5-10 versus 11-20 brain metastases: a retrospective cohort study combining 2 databases totaling 2319 patients. World Neurosurg 2021; 146: e479-e491
    CrossrefPubMedSearch in Google Scholar
  • 27 Balasubramanian SK, Sharma M, Venur VA. et al. Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis. Neuro-oncol 2020; 22 (02) 267-277
    PubMedSearch in Google Scholar
  • 28 Li J, Ludmir EB, Wang Y. et al. Stereotactic radiosurgery versus whole-brain radiation therapy for patients with 4–15 brain metastases: a phase III randomized controlled trial. Int J Radiat Oncol Biol Phys 2020; 108 (03) S21-S22
    CrossrefPubMedSearch in Google Scholar
  • 29 Ammirati M, Nahed BV, Andrews D, Chen CC, Olson JJ. Congress of neurological surgeons systematic review and evidence-based guidelines on treatment options for adults with multiple metastatic brain tumors. Neurosurgery 2019; 84 (03) E180-E182
    CrossrefPubMedSearch in Google Scholar
  • 30 Borius PY, Régis J, Carpentier A, Kalamarides M, Valery CA, Latorzeff I. Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. Cancer Metastasis Rev 2021; 40 (01) 341-354
    CrossrefPubMedSearch in Google Scholar
  • 31 Chen L, Douglass J, Kleinberg 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 2018; 100 (04) 916-925
    CrossrefPubMedSearch in Google Scholar
  • 32 Kim AH, Tatter S, Rao G. et al. Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-month outcomes and quality of life after brain tumor ablation. Neurosurgery 2020; 87 (03) E338-E346
    CrossrefPubMedSearch in Google Scholar
  • 33 Ahluwalia M, Barnett GH, Deng D. et al. Laser ablation after stereotactic radiosurgery: a multicenter prospective study in patients with metastatic brain tumors and radiation necrosis. J Neurosurg 2018; 130 (03) 804-811
    CrossrefPubMedSearch in Google Scholar
  • 34 Shah AH, Semonche A, Eichberg DG. et al. The role of laser interstitial thermal therapy in surgical neuro-oncology: series of 100 consecutive patients. Neurosurgery 2020; 87 (02) 266-275
    CrossrefPubMedSearch in Google Scholar
  • 35 Bastos DCA, Rao G, Oliva ICG. et al. Predictors of local control of brain metastasis treated with laser interstitial thermal therapy. Neurosurgery 2020; 87 (01) 112-122
    CrossrefPubMedSearch in Google Scholar
  • 36 Alattar AA, Bartek Jr J, Chiang VL. et al. Stereotactic laser ablation as treatment of brain metastases recurring after stereotactic radiosurgery: a systematic literature review. World Neurosurg 2019; 128: 134-142
    CrossrefPubMedSearch in Google Scholar
  • 37 Leuthardt EC, Duan C, Kim MJ. et al. Hyperthermic laser ablation of recurrent glioblastoma leads to temporary disruption of the peritumoral blood brain barrier. PLoS One 2016; 11 (02) e0148613
    CrossrefPubMedSearch in Google Scholar
  • 38 Meng Y, Pople CB, Budiansky D. et al. Current state of therapeutic focused ultrasound applications in neuro-oncology. J Neurooncol 2022; 156 (01) 49-59
    CrossrefPubMedSearch in Google Scholar
  • 39 Meng Y, Suppiah S, Surendrakumar S, Bigioni L, Lipsman N. Low-intensity MR-guided focused ultrasound mediated disruption of the blood-brain barrier for intracranial metastatic diseases. Front Oncol 2018; 8: 338
    CrossrefPubMedSearch in Google Scholar
  • 40 Maier-Hauff K, Ulrich F, Nestler D. et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neurooncol 2011; 103 (02) 317-324
    CrossrefPubMedSearch in Google Scholar
  • 41 Chitgupi U, Qin Y, Lovell JF. Targeted nanomaterials for phototherapy. Nanotheranostics 2017; 1 (01) 38-58
    CrossrefPubMedSearch in Google Scholar
  • 42 Cortes J, Rodriguez J, Aramendia JM. et al. Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology 2003; 64 (01) 28-35
    CrossrefPubMedSearch in Google Scholar
  • 43 Dinglin XX, Huang Y, Liu H, Zeng YD, Hou X, Chen LK. Pemetrexed and cisplatin combination with concurrent whole brain radiotherapy in patients with brain metastases of lung adenocarcinoma: a single-arm phase II clinical trial. J Neurooncol 2013; 112 (03) 461-466
    CrossrefPubMedSearch in Google Scholar
  • 44 Nayak L, DeAngelis LM, Robins HI. et al. Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. Cancer 2015; 121 (23) 4165-4172
    CrossrefPubMedSearch in Google Scholar
  • 45 Chevallier M, Borgeaud M, Addeo A, Friedlaender A. Oncogenic driver mutations in non-small cell lung cancer: past, present and future. World J Clin Oncol 2021; 12 (04) 217-237
    CrossrefPubMedSearch in Google Scholar
  • 46 Raez LE, Cardona AF, Arrieta O, Lopes G. Lung cancer disparities in Hispanics: molecular diagnosis and use of immunotherapy. JCO Glob Oncol 2020; 6 (06) 784-788
    CrossrefPubMedSearch in Google Scholar
  • 47 Deng Y, Feng W, Wu J. et al. The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer. Mol Clin Oncol 2014; 2 (01) 116-120
    CrossrefPubMedSearch in Google Scholar
  • 48 Welsh JW, Komaki R, Amini A. et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol 2013; 31 (07) 895-902
    CrossrefPubMedSearch in Google Scholar
  • 49 Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crinò L, Villa E. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 2004; 15 (07) 1042-1047
    CrossrefPubMedSearch in Google Scholar
  • 50 Hou X, Li M, Wu G. et al. Gefitinib plus chemotherapy vs gefitinib alone in untreated EGFR-mutant non-small cell lung cancer in patients with brain metastases: the GAP BRAIN Open-Label, Randomized, Multicenter, Phase 3 Study. JAMA Netw Open 2023; 6 (02) e2255050
    CrossrefPubMedSearch in Google Scholar
  • 51 Kiura K, Yoh K, Katakami N. et al. Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples. Cancer Sci 2018; 109 (04) 1177-1184
    CrossrefPubMedSearch in Google Scholar
  • 52 Reungwetwattana T, Nakagawa K, Cho BC. 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 2018; 36 (33) JCO2018783118
    CrossrefPubMedSearch in Google Scholar
  • 53 Du X, Shao Y, Qin H-F, Tai Y-H, Gao H-J. ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thorac Cancer 2018; 9 (04) 423-430
    CrossrefPubMedSearch in Google Scholar
  • 54 Solomon BJ, Cappuzzo F, Felip E. 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 2016; 34 (24) 2858-2865
    CrossrefPubMedSearch in Google Scholar
  • 55 Peters S, Camidge DR, Shaw AT. et al; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017; 377 (09) 829-838
    CrossrefPubMedSearch in Google Scholar
  • 56 Camidge DR, Kim HR, Ahn MJ. et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol 2020; 38 (31) 3592-3603
    CrossrefPubMedSearch in Google Scholar
  • 57 Soria JC, Tan DSW, Chiari R. et al. 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 2017; 389 (10072): 917-929
    CrossrefPubMedSearch in Google Scholar
  • 58 Shaw AT, Bauer TM, de Marinis F. et al; CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med 2020; 383 (21) 2018-2029
    CrossrefPubMedSearch in Google Scholar
  • 59 Yang Y, Zhou J, Zhou J. et al. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir Med 2020; 8 (01) 45-53
    CrossrefPubMedSearch in Google Scholar
  • 60 Ferrara R, Auger N, Auclin E, Besse B. Clinical and translational implications of RET rearrangements in non-small cell lung cancer. J Thorac Oncol 2018; 13 (01) 27-45
    CrossrefPubMedSearch in Google Scholar
  • 61 Subbiah V, Gainor JF, Oxnard GR. et al. Intracranial efficacy of selpercatinib in RET fusion-positive non-small cell lung cancers on the LIBRETTO-001 trial. Clin Cancer Res 2021; 27 (15) 4160-4167
    CrossrefPubMedSearch in Google Scholar
  • 62 Gainor JF, Curigliano G, Kim DW. et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol 2021; 22 (07) 959-969
    CrossrefPubMedSearch in Google Scholar
  • 63 Planchard D, Kim TM, Mazieres J. et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 2016; 17 (05) 642-650
    CrossrefPubMedSearch in Google Scholar
  • 64 Riely GJ, Ahn MJ, Felip E. et al. Encorafenib plus binimetinib in patients with BRAF V600-mutant non-small cell lung cancer: phase II PHAROS study design. Future Oncol 2022; 18 (07) 781-791
    CrossrefPubMedSearch in Google Scholar
  • 65 Addeo A, Banna GL, Friedlaender A. KRAS G12C mutations in NSCLC: from target to resistance. Cancers (Basel) 2021; 13 (11) 2541
    CrossrefPubMedSearch in Google Scholar
  • 66 Nakajima EC, Drezner N, Li X. et al. FDA approval summary: sotorasib for KRAS G12C-mutated metastatic NSCLC. Clin Cancer Res 2022; 28 (08) 1482-1486
    CrossrefPubMedSearch in Google Scholar
  • 67 Ramalingam S, Skoulidis F, Govindan R. et al. P52.03 efficacy of sotorasib in KRAS p.G12C-mutated NSCLC with stable brain metastases: a post-hoc analysis of CodeBreaK 100. J Thorac Oncol 2021; 16 (10, suppl): S1123
    CrossrefPubMedSearch in Google Scholar
  • 68 Sabari JK, Velcheti V, Shimizu K. et al. Activity of Adagrasib (MRTX849) in brain metastases: preclinical models and clinical data from patients with KRASG12C-mutant non-small cell lung cancer. Clin Cancer Res 2022; 28 (15) 3318-3328
    CrossrefPubMedSearch in Google Scholar
  • 69 Jänne PA, Riely GJ, Gadgeel SM. et al. Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation. N Engl J Med 2022; 387 (02) 120-131
    CrossrefPubMedSearch in Google Scholar
  • 70 Paik PK, Felip E, Veillon R. et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020; 383 (10) 931-943
    CrossrefPubMedSearch in Google Scholar
  • 71 Patil T, Smith DE, Bunn PA. et al. The incidence of brain metastases in stage IV ROS1-rearranged non-small cell lung cancer and rate of central nervous system progression on crizotinib. J Thorac Oncol 2018; 13 (11) 1717-1726
    CrossrefPubMedSearch in Google Scholar
  • 72 Drilon A, Chiu CH, Fan Y. et al. Long-term efficacy and safety of entrectinib in ROS1 fusion-positive NSCLC. JTO Clin Res Rep 2022; 3 (06) 100332
    PubMedSearch in Google Scholar
  • 73 Cho BC, Drilon AE, Doebele RC. et al. Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer (TRIDENT-1 study). J Clin Oncol 2019; 37 (15, suppl): 9011
    CrossrefPubMedSearch in Google Scholar
  • 74 Drilon AE, Cho BC, Felip E. et al. Intracranial and systemic efficacy of repotrectinib in advanced ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) and central nervous system metastases (CNS mets) in the phase 1/2 TRIDENT-1. J Clin Oncol 2023; 41 (16, suppl): 9017
    CrossrefPubMedSearch in Google Scholar
  • 75 Baraibar I, Mezquita L, Gil-Bazo I, Planchard D. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Crit Rev Oncol Hematol 2020; 148: 102906
    CrossrefPubMedSearch in Google Scholar
  • 76 Le X, Cornelissen R, Garassino M. et al. Poziotinib in non-small-cell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 trial. J Clin Oncol 2022; 40 (07) 710-718
    CrossrefPubMedSearch in Google Scholar
  • 77 Le X, Garassino MC, Cornelissen R. et al. CNS activity of poziotinib in NSCLC with exon 20 insertion mutations. J Clin Oncol 2021; 39 (15, suppl): 9093
    CrossrefPubMedSearch in Google Scholar
  • 78 Drilon A, Tan DSW, Lassen UN. et al. Efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase fusion-positive lung cancers. JCO Precis Oncol 2022; 6 (06) e2100418
    CrossrefPubMedSearch in Google Scholar
  • 79 Hong DS, DuBois SG, Kummar S. et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21 (04) 531-540
    CrossrefPubMedSearch in Google Scholar
  • 80 Drilon A, Paz-Ares L, Doebele RC. et al. 543P entrectinib in NTRK fusion-positive NSCLC: updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372–001. Ann Oncol 2020;31:S474-S-47-5
    PubMed
  • 81 Goldberg SB, Schalper KA, Gettinger SN. 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 2020; 21 (05) 655-663
    CrossrefPubMedSearch in Google Scholar
  • 82 Frost N, Kollmeier J, Misch D. et al. Pembrolizumab as first-line palliative therapy in PD-L1 overexpressing (≥ 50%) NSCLC: real-world results with special focus on PS ≥ 2, brain metastases, and steroids. Clin Lung Cancer 2021; 22 (05) 411-422
    CrossrefPubMedSearch in Google Scholar
  • 83 Gadgeel SM, Lukas RV, Goldschmidt J. 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 2019; 128: 105-112
    CrossrefPubMedSearch in Google Scholar
  • 84 Patel P, Alrifai D, McDonald F, Forster M. AstraZeneca UK Limited. Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). Br J Cancer 2020; 123 (Suppl. 01) 18-27
    CrossrefPubMedSearch in Google Scholar
  • 85 Giaquinto AN, Sung H, Miller KD. et al. Breast Cancer Statistics, 2022. CA Cancer J Clin 2022; 72 (06) 524-541
    CrossrefPubMedSearch in Google Scholar
  • 86 Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339 (22) 1609-1618
    CrossrefPubMedSearch in Google Scholar
  • 87 Graeber MB, Scheithauer BW, Kreutzberg GW. Microglia in brain tumors. Glia 2002; 40 (02) 252-259
    CrossrefPubMedSearch in Google Scholar
  • 88 Watters JJ, Schartner JM, Badie B. Microglia function in brain tumors. J Neurosci Res 2005; 81 (03) 447-455
    CrossrefPubMedSearch in Google Scholar
  • 89 Pukrop T, Dehghani F, Chuang H-N. et al. Microglia promote colonization of brain tissue by breast cancer cells in a Wnt-dependent way. Glia 2010; 58 (12) 1477-1489
    CrossrefPubMedSearch in Google Scholar
  • 90 Ma G, He J, Yu Y. et al. Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation. Int J Biol Sci 2015; 11 (05) 618-628
    CrossrefPubMedSearch in Google Scholar
  • 91 Bergen ES, Berghoff AS, Medjedovic M. et al. Continued endocrine therapy is associated with improved survival in patients with breast cancer brain metastases. Clin Cancer Res 2019; 25 (09) 2737-2744
    CrossrefPubMedSearch in Google Scholar
  • 92 Modi S, Jacot W, Yamashita T. et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022; 387 (01) 9-20
    CrossrefPubMedSearch in Google Scholar
  • 93 Vogel CL, Cobleigh MA, Tripathy D. et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20 (03) 719-726
    CrossrefPubMedSearch in Google Scholar
  • 94 Park YH, Park MJ, Ji SH. et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer 2009; 100 (06) 894-900
    CrossrefPubMedSearch in Google Scholar
  • 95 Lin NU, Pegram M, Sahebjam S. et al. Pertuzumab plus high-dose trastuzumab in patients with progressive brain metastases and HER2-positive metastatic breast cancer: primary analysis of a phase II study. J Clin Oncol 2021; 39 (24) 2667-2675
    CrossrefPubMedSearch in Google Scholar
  • 96 Jacot W, Pons E, Frenel JS. et al. Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res Treat 2016; 157 (02) 307-318
    CrossrefPubMedSearch in Google Scholar
  • 97 Fabi A, Alesini D, Valle E. et al. T-DM1 and brain metastases: clinical outcome in HER2-positive metastatic breast cancer. Breast 2018; 41: 137-143
    CrossrefPubMedSearch in Google Scholar
  • 98 Montemurro F, Delaloge S, Barrios CH. et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆ . Ann Oncol 2020; 31 (10) 1350-1358
    CrossrefPubMedSearch in Google Scholar
  • 99 Krop IE, Lin NU, Blackwell K. et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol 2015; 26 (01) 113-119
    CrossrefPubMedSearch in Google Scholar
  • 100 Jerusalem G, Park YH, Yamashita T, Hurvitz SA, Modi S, Andre F, Krop IE, Gonzàlez Farré X, You B, Saura C, Kim SB, Osborne CR, Murthy RK, Gianni L, Takano T, Liu Y, Cathcart J, Lee C, Perrin C. Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis. Cancer Discov 2022; Dec 2; 12 (12) 2754-2762
    CrossrefPubMedSearch in Google Scholar
  • 101 Cortés J, Kim SB, Chung WP. et al; DESTINY-Breast03 Trial Investigators. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med 2022; 386 (12) 1143-1154
    CrossrefPubMedSearch in Google Scholar
  • 102 Bartsch R, Berghoff AS, Furtner J. et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med 2022; 28 (09) 1840-1847
    CrossrefPubMedSearch in Google Scholar
  • 103 Pérez-García JM, Vaz Batista M, Cortez P. et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial. Neuro-oncol 2023; 25 (01) 157-166
    CrossrefPubMedSearch in Google Scholar
  • 104 Lockman PR, Mittapalli RK, Taskar KS. et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res 2010; 16 (23) 5664-5678
    CrossrefPubMedSearch in Google Scholar
  • 105 Lin NU, Murthy RK, Abramson V. et al. Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: updated exploratory analysis of the HER2CLIMB randomized clinical trial. JAMA Oncol 2023; 9 (02) 197-205
    CrossrefPubMedSearch in Google Scholar
  • 106 Bachelot T, Romieu G, Campone M. 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 2013; 14 (01) 64-71
    CrossrefPubMedSearch in Google Scholar
  • 107 Lin NU, Diéras V, Paul D. et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 2009; 15 (04) 1452-1459
    CrossrefPubMedSearch in Google Scholar
  • 108 Seligmann JF, Wright-Hughes A, Pottinger A. et al. Lapatinib plus capecitabine versus trastuzumab plus capecitabine in the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer with central nervous system metastases for patients currently or previously treated with trastuzumab (LANTERN): a phase II randomised trial. Clin Oncol (R Coll Radiol) 2020; 32 (10) 656-664
    CrossrefPubMedSearch in Google Scholar
  • 109 Yan M, Ouyang Q, Sun T. et al. Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial. Lancet Oncol 2022; 23 (03) 353-361
    CrossrefPubMedSearch in Google Scholar
  • 110 Dirix LY, Takacs I, Jerusalem G. et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat 2018; 167 (03) 671-686
    CrossrefPubMedSearch in Google Scholar
  • 111 Cortes J, Cescon DW, Rugo HS. et al; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 2020; 396 (10265): 1817-1828
    CrossrefPubMedSearch in Google Scholar
  • 112 Schmid P, Adams S, Rugo HS. et al; IMpassion130 Trial Investigators. Atezolizumab and Nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018; 379 (22) 2108-2121
    CrossrefPubMedSearch in Google Scholar
  • 113 Rishi A, Yu HM. Current treatment of melanoma brain metastasis. Curr Treat Options Oncol 2020; 21 (06) 45
    CrossrefPubMedSearch in Google Scholar
  • 114 Margolin K, Atkins B, Thompson A. et al. Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group. J Cancer Res Clin Oncol 2002; 128 (04) 214-218
    CrossrefPubMedSearch in Google Scholar
  • 115 Jacquillat C, Khayat D, Banzet P. et al. Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. Cancer 1990; 66 (09) 1873-1878
    CrossrefPubMedSearch in Google Scholar
  • 116 Sala E, Mologni L, Truffa S, Gaetano C, Bollag GE, Gambacorti-Passerini C. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res 2008; 6 (05) 751-759
    CrossrefPubMedSearch in Google Scholar
  • 117 Dummer R, Goldinger SM, Turtschi CP. 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 2014; 50 (03) 611-621
    CrossrefPubMedSearch in Google Scholar
  • 118 McArthur GA, Maio M, Arance A. et al. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol 2017; 28 (03) 634-641
    CrossrefPubMedSearch in Google Scholar
  • 119 Long GV, Trefzer U, Davies MA. 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 2012; 13 (11) 1087-1095
    CrossrefPubMedSearch in Google Scholar
  • 120 Davies MA, Saiag P, Robert C. et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 2017; 18 (07) 863-873
    CrossrefPubMedSearch in Google Scholar
  • 121 Syeda MM, Wiggins JM, Corless BC. et al. Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or dabrafenib plus trametinib: a clinical validation study. Lancet Oncol 2021; 22 (03) 370-380
    CrossrefPubMedSearch in Google Scholar
  • 122 Dummer R, Ascierto PA, Gogas HJ. et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2018; 19 (05) 603-615
    CrossrefPubMedSearch in Google Scholar
  • 123 Holbrook K, Lutzky J, Davies MA. et al. Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: a case series. Cancer 2020; 126 (03) 523-530
    CrossrefPubMedSearch in Google Scholar
  • 124 Tarhini AA, Iqbal F. CTLA-4 blockade: therapeutic potential in cancer treatments. OncoTargets Ther 2010; 3: 15-25
    CrossrefPubMedSearch in Google Scholar
  • 125 Margolin K, Ernstoff MS, Hamid O. et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 2012; 13 (05) 459-465
    CrossrefPubMedSearch in Google Scholar
  • 126 Tawbi HA, Forsyth PA, Algazi A. et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med 2018; 379 (08) 722-730
    CrossrefPubMedSearch in Google Scholar
  • 127 Long GV, Atkinson V, Lo S. et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 2018; 19 (05) 672-681
    CrossrefPubMedSearch in Google Scholar
  • 128 Kluger HM, Chiang V, Mahajan A. et al. Long-term survival of patients with melanoma with active brain metastases treated with pembrolizumab on a phase II trial. J Clin Oncol 2019; 37 (01) 52-60
    CrossrefPubMedSearch in Google Scholar