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American Journal of Clinical Dermatology
Published in: American Journal of Clinical Dermatology 4/2022

09-05-2022 | Metastasis | Review Article

Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents

Author: Stergios J. Moschos

Published in: American Journal of Clinical Dermatology | Issue 4/2022

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Abstract

Brain metastases from melanoma are no longer uniformly associated with dismal outcomes. Impressive tumor tissue-based (craniotomy) translational research has consistently shown that distinct patient subgroups may have a favorable prognosis. This review provides a historical overview of the standard-of-care treatments until the early 2010s. It subsequently summarizes more recent advances in understanding the biology of melanoma brain metastases (MBMs) and treating patients with MBMs, mainly focusing upon prospective clinical trials of BRAF/MEK and PD-1/CTLA-4 inhibitors in patients with previously untreated MBMs. These additional systemic treatments have provided effective complementary treatment approaches and/or alternatives to radiation and craniotomy. The current role of radiation therapy, especially in conjunction with systemic therapies, is also discussed through the lens of various retrospective studies. The combined efficacy of systemic treatments with radiation has improved overall survival over the last 10 years and has sparked considerable research interest regarding optimal dosing and sequencing of radiation treatments with systemic treatments. Finally, the review describes ongoing clinical trials in patients with MBMs.
Literature
1.
Cohen JV, Tawbi H, Margolin KA, et al. Melanoma central nervous system metastases: current approaches, challenges, and opportunities. Pigment Cell Melanoma Res. 2016;29:627–42.PubMedPubMedCentralCrossRef
2.
Karachaliou GS, Alkallas R, Carroll SB, et al. The clinical significance of adenomatous polyposis coli (APC) and catenin beta 1 (CTNNB1) genetic aberrations in patients with melanoma. BMC Cancer. 2022;22:38.PubMedPubMedCentralCrossRef
3.
Davies MA, Liu P, McIntyre S, et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011;117:1687–96.PubMedCrossRef
4.
Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. Cancer J Clin. 2017;67:472–92.CrossRef
5.
Kondziolka D, Bernstein M, Resch L, et al. Significance of hemorrhage into brain tumors: clinicopathological study. J Neurosurg. 1987;67:852–7.PubMedCrossRef
6.
Agarwala SS, Kirkwood JM, Gore M, et al. Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. J Clin Oncol. 2004;22:2101–7.PubMedCrossRef
7.
Guirguis LM, Yang JC, White DE, et al. Safety and efficacy of high-dose interleukin-2 therapy in patients with brain metastases. J Immunother. 2002;25:82–7.PubMedPubMedCentralCrossRef
8.
Hong AM, Fogarty GB, Dolven-Jacobsen K, et al. Adjuvant whole-brain radiation therapy compared with observation after local treatment of melanoma brain metastases: a multicenter, randomized phase III trial. J Clin Oncol. 2019;37:3132–41.PubMedCrossRef
9.
Sperduto PW, Shanley R, Luo X, et al. Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1–3 brain metastases; poststratified by the graded prognostic assessment (GPA). Int J Radiat Oncol Biol Phys. 2014;90:526–31.PubMedPubMedCentralCrossRef
10.
Brown PD, Jaeckle K, Ballman KV, et al. 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. 2016;316:401–9.PubMedPubMedCentralCrossRef
11.
Sampson JH, Carter JH Jr, Friedman AH, et al. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg. 1998;88:11–20.PubMedCrossRef
12.
Hamilton R, Krauze M, Romkes M, et al. Pathologic and gene expression features of metastatic melanomas to the brain. Cancer. 2013;119:2737–46.PubMedCrossRef
13.
Eigentler TK, Figl A, Krex D, et al. Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma. Cancer. 2011;117:1697–703.PubMedCrossRef
14.
Raizer JJ, Hwu WJ, Panageas KS, et al. Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro Oncol. 2008;10:199–207.PubMedPubMedCentralCrossRef
15.
Zakrzewski J, Geraghty LN, Rose AE, et al. Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastases and post-brain metastases survival. Cancer. 2011;117:1711–20.PubMedCrossRef
16.
Wang E, Miller LD, Ohnmacht GA, et al. Prospective molecular profiling of melanoma metastases suggests classifiers of immune responsiveness. Cancer Res. 2002;62:3581–6.PubMedPubMedCentral
17.
18.
Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst. 2006;98:472–82.PubMedCrossRef
19.
Network CGA. Genomic classification of cutaneous melanoma. Cell. 2015;161:1681–96.CrossRef
20.
Shain AH, Joseph NM, Yu R, et al. Genomic and transcriptomic analysis reveals incremental disruption of key signaling pathways during melanoma evolution. Cancer Cell. 2018;34:45-55.e4.PubMedPubMedCentralCrossRef
21.
Colombino M, Capone M, Lissia A, et al. BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. J Clin Oncol. 2012;30:2522–9.PubMedCrossRef
22.
Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29:1239–46.PubMedCrossRef
23.
Rodewald A-K, et al. Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis. J Cutan Pathol. 2019;46(8):570–8, PMID 30927294. https://​doi.​org/​10.​1111/​cup.​13465.
24.
Trembath DG, Davis ES, Rao S, et al. Brain tumor microenvironment and angiogenesis in melanoma brain metastases. Front Oncol. 2020;10:604213.PubMedCrossRef
25.
Berghoff AS, Fuchs E, Ricken G, et al. Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases. Oncoimmunology. 2016;5:e1057388.PubMedCrossRef
26.
Kluger HM, Zito CR, Barr ML, et al. Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clin Cancer Res. 2015;21:3052–60.PubMedPubMedCentralCrossRef
27.
Fischer GM, Jalali A, Kircher DA, et al. Molecular profiling reveals unique immune and metabolic features of melanoma brain metastases. Cancer Discov. 2019;9:628–45.PubMedPubMedCentralCrossRef
28.
Tran TT, Mahajan A, Chiang VL, et al. Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy. J Immunother Cancer. 2019;7:200.PubMedPubMedCentralCrossRef
29.
Herrera-Rios D, Mughal SS, Teuber-Hanselmann S, et al. Macrophages/microglia represent the major source of indolamine 2,3-dioxygenase expression in melanoma metastases of the brain. Front Immunol. 2020;11:120.PubMedPubMedCentralCrossRef
30.
Trembath DG, Ivanova A, Krauze MT, et al. Melanoma-specific expression of the tumor suppressor proteins p16 and PTEN is a favorable prognostic factor in established melanoma brain metastases. Melanoma Res. 2021;31:264–7.PubMedPubMedCentralCrossRef
31.
Varaljai R, Horn S, Sucker A, et al. Integrative genomic analyses of patient-matched intracranial and extracranial metastases reveal a novel brain-specific landscape of genetic variants in driver genes of malignant melanoma. Cancers (Basel). 2021;13:731.PubMedPubMedCentralCrossRef
32.
Brastianos PK, Carter SL, Santagata S, et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov. 2015;5:1164–77.PubMedPubMedCentralCrossRef
33.
Fang P, Boehling NS, Koay EJ, et al. Melanoma brain metastases harboring BRAF (V600K) or NRAS mutations are associated with an increased local failure rate following conventional therapy. J Neurooncol. 2018;137:67–75.PubMedCrossRef
34.
Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381:1535–46.PubMedCrossRef
35.
Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381:626–36.PubMedCrossRef
36.
Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867–76.PubMedCrossRef
37.
Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.PubMedCrossRef
38.
Dummer R, Ascierto PA, Gogas HJ, et al. Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19:1315–27.PubMedCrossRef
39.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New Response Evaluation Criteria in Solid Tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRef
40.
Lin NU, Lee EQ, Aoyama H, et al. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015;16:e270–8.PubMedCrossRef
41.
Chamberlain M, Junck L, Brandsma D, et al. Leptomeningeal metastases: a RANO proposal for response criteria. Neuro Oncol. 2017;19:484–92.PubMed
42.
Griffith JI, Rathi S, Zhang W, et al. Addressing BBB heterogeneity: a new paradigm for drug delivery to brain tumors. Pharmaceutics. 2020;12:1205.PubMedCentralCrossRef
43.
Vaidhyanathan S, Mittapalli RK, Sarkaria JN, et al. Factors influencing the CNS distribution of a novel MEK-1/2 inhibitor: implications for combination therapy for melanoma brain metastases. Drug Metab Dispos. 2014;42:1292–300.PubMedPubMedCentralCrossRef
44.
Mittapalli RK, Vaidhyanathan S, Dudek AZ, et al. 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. 2013;344:655–64.PubMedPubMedCentralCrossRef
45.
Falchook GS, Long GV, Kurzrock R, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 2012;379:1893–901.PubMedPubMedCentralCrossRef
46.
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;13:1087–95.PubMedCrossRef
47.
Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380:358–65.PubMedCrossRef
48.
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;28:634–41.PubMedCrossRef
49.
Sakji-Dupre L, Le Rhun E, Templier C, et al. Cerebrospinal fluid concentrations of vemurafenib in patients treated for brain metastatic BRAF-V600 mutated melanoma. Melanoma Res. 2015;25:302–5.PubMedCrossRef
50.
51.
Flaherty K, Davies MA, Grob JJ, et al. Genomic analysis and 3-y efficacy and safety update of COMBI-d: A phase 3 study of dabrafenib (D) + trametinib (T) vs D monotherapy in patients (pts) with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma (abstract 9502). ASCO Annual Meeting; Chicago (IL). 2016.
52.
Davies MA, Saiag P, Robert C, 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. 2017;18:863–73.PubMedPubMedCentralCrossRef
53.
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;126:523–30.PubMedCrossRef
54.
Ascierto PA, Dummer R, Gogas HJ, et al. Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. Eur J Cancer. 2020;126:33–44.PubMedCrossRef
55.
Delord JP, Robert C, Nyakas M, et al. Phase I dose-escalation and -expansion study of the BRAF inhibitor encorafenib (LGX818) in metastatic BRAF-mutant melanoma. Clin Cancer Res. 2017;23:5339–48.PubMedCrossRef
56.
IMarquez-Rodas I, Arance A, Berciano Guerrero MA, et al. Intracranial activity of encorafenib and binimetinib followed by radiotherapy in patients with BRAF mutated melanoma and brain metastasis: preliminary results of the GEM1802/EBRAIN-MEL phase II clinical trial (abstract 1038MO). In: ESMO Congress Virtual Meeting; 2021
57.
Goldinger SM, Valeska Matter A, Urner-Bloch U, et al. Binimetinib in heavily pretreated patients with NRAS-mutant melanoma with brain metastases. Br J Dermatol. 2020;182:488–90.PubMedCrossRef
58.
Amaral T, Niessner H, Sinnberg T, et al. An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery-the BUMPER study. Neurooncol Adv. 2020;2:vdaa140.PubMedPubMedCentral
59.
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;13:459–65.PubMedCrossRef
60.
Weber JS, Amin A, Minor D, et al. Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial. Melanoma Res. 2011;21:530–4.PubMedCrossRef
61.
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;37:52–60.PubMedCrossRef
62.
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;19:672–81.PubMedCrossRef
63.
Tawbi HA, Forsyth PA, Hodi FS, et al. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021;23:1961–73.PubMedPubMedCentralCrossRef
64.
Tawbi HA, et al. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol 2021;22(12):1692–1704. PMID 34774225. https://​doi.​org/​10.​1016/​S1470-2045(21)00545-3.
65.
Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, et al. Primary analysis and 4-year follow-up of the phase III NIBIT-M2 trial in melanoma patients with brain metastases. Clin Cancer Res. 2021;27:4737–45.PubMedCrossRef
66.
Atkins MB, Lee SJ, Chmielowski B, et al. DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): a phase III trial: ECOG-ACRIN EA6134 (abstract 356154). In: ASCO Monthly Plenary Series; 2021.
67.
Powell S, Dudek AZ. Single-institution outcome of high-dose interleukin-2 (HD IL-2) therapy for metastatic melanoma and analysis of favorable response in brain metastases. Anticancer Res. 2009;29:4189–93.PubMed
68.
Mehta GU, Malekzadeh P, Shelton T, et al. Outcomes of adoptive cell transfer with tumor-infiltrating lymphocytes for metastatic melanoma patients with and without brain metastases. J Immunother. 2018;41:241–7.PubMedPubMedCentralCrossRef
69.
Vosoughi E, Lee JM, Miller JR, et al. Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies. BMC Cancer. 2018;18:490.PubMedPubMedCentralCrossRef
70.
Kruser TJ, Gondi V, Sperduto PW, et al. Omitting radiosurgery in melanoma brain metastases: a drastic and dangerous de-escalation. Lancet Oncol. 2018;19:e366.PubMedCrossRef
71.
Franceschini D, Franzese C, Navarria P, et al. Radiotherapy and immunotherapy: can this combination change the prognosis of patients with melanoma brain metastases? Cancer Treat Rev. 2016;50:1–8.PubMedCrossRef
72.
Knisely JP, Yu JB, Flanigan J, et al. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117:227–33.PubMedPubMedCentralCrossRef
73.
74.
Schmidberger H, Rapp M, Ebersberger A, et al. Long-term survival of patients after ipilimumab and hypofractionated brain radiotherapy for brain metastases of malignant melanoma: sequence matters. Strahlenther Onkol. 2018;194:1144–51.PubMedPubMedCentralCrossRef
75.
Anderson ES, Postow MA, Wolchok JD, et al. Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. J Immunother Cancer. 2017;5:76.PubMedPubMedCentralCrossRef
76.
Martins F, Schiappacasse L, Levivier M, et al. The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study. J Neurooncol. 2020;146:181–93.PubMedCrossRef
77.
Schaule J, Kroeze SGC, Blanck O, et al. Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy: melanoma brain metastases prognostic score. Radiat Oncol. 2020;15:135.PubMedPubMedCentralCrossRef
78.
Ahmed KA, Abuodeh YA, Echevarria MI, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. Ann Oncol. 2016;27:2288–94.PubMedPubMedCentralCrossRef
79.
Carron R, Gaudy-Marqueste C, Amatore F, et al. Stereotactic radiosurgery combined with anti-PD1 for the management of melanoma brain metastases: a retrospective study of safety and efficacy. Eur J Cancer. 2020;135:52–61.PubMedCrossRef
80.
Gerber NK, Young RJ, Barker CA, et al. Ipilimumab and whole brain radiation therapy for melanoma brain metastases. J Neurooncol. 2015;121:159–65.PubMedCrossRef
81.
Mathew M, Tam M, Ott PA, et al. Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery. Melanoma Res. 2013;23:191–5.PubMedCrossRef
82.
Liermann J, Winkler JK, Syed M, et al. Stereotactic radiosurgery with concurrent immunotherapy in melanoma brain metastases is feasible and effective. Front Oncol. 2020;10:592796.PubMedPubMedCentralCrossRef
83.
Robin TP, Breeze RE, Smith DE, et al. Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases. J Neurooncol. 2018;140:55–62.PubMedPubMedCentralCrossRef
84.
Wegner RE, Abel S, D’Amico RS, et al. Time from stereotactic radiosurgery to immunotherapy in patients with melanoma brain metastases and impact on outcome. J Neurooncol. 2021;152:79–87.PubMedCrossRef
85.
Amaral T, Tampouri I, Eigentler T, et al. Immunotherapy plus surgery/radiosurgery is associated with favorable survival in patients with melanoma brain metastasis. Immunotherapy. 2019;11:297–309.PubMedCrossRef
86.
Gatterbauer B, Hirschmann D, Eberherr N, et al. Toxicity and efficacy of Gamma knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy: a retrospective cohort study. Cancer Med. 2020;9:4026–36.PubMedPubMedCentralCrossRef
87.
Diao K, Bian SX, Routman DM, et al. Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity. J Neurooncol. 2018;139:421–9.PubMedPubMedCentralCrossRef
88.
Rauschenberg R, Bruns J, Brutting J, et al. Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases. Eur J Cancer. 2019;110:11–20.PubMedCrossRef
89.
Gabani P, Fischer-Valuck BW, Johanns TM, et al. Stereotactic radiosurgery and immunotherapy in melanoma brain metastases: patterns of care and treatment outcomes. Radiother Oncol. 2018;128:266–73.PubMedCrossRef
90.
Kaidar-Person O, Zagar TM, Deal A, et al. The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy. Anticancer Drugs. 2017;28:669–75.PubMedCrossRef
91.
Amaral T, Kiecker F, Schaefer S, et al. Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients. J Immunother Cancer. 2020;8:e000333.PubMedPubMedCentralCrossRef
92.
Kennedy WR, DeWees TA, Acharya S, et al. Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery. J Neurosurg. 2020;2020:1–7.
93.
Morisada M, Clavijo PE, Moore E, et al. PD-1 blockade reverses adaptive immune resistance induced by high-dose hypofractionated but not low-dose daily fractionated radiation. Oncoimmunology. 2018;7:e1395996.PubMedCrossRef
94.
Savage T, Pandey S, Guha C. Postablation modulation after single high-dose radiation therapy improves tumor control via enhanced immunomodulation. Clin Cancer Res. 2020;26:910–21.PubMedCrossRef
95.
Khan MK, Nasti T, Yushak ML, et al. Interim results of prospective pilot phase II trial of concurrent anti-PD-1 and stereotactic radiosurgery (SRS) for melanoma and NSCLC patients with brain metastases (NCT02858869, abstract e22002). ASCO Scientific Virtual Program; 2020.
96.
Glitza IC, Smalley KSM, Brastianos PK, et al. Leptomeningeal disease in melanoma patients: an update to treatment, challenges, and future directions. Pigment Cell Melanoma Res. 2020;33:527–41.PubMedCrossRef
97.
Smalley I, Chen Z, Phadke M, et al. Single-cell characterization of the immune microenvironment of melanoma brain and leptomeningeal metastases. Clin Cancer Res. 2021;27:4109–25.PubMedPubMedCentralCrossRef
98.
Smalley I, Law V, Wyatt C, et al. Proteomic analysis of CSF from patients with leptomeningeal melanoma metastases identifies signatures associated with disease progression and therapeutic resistance. Clin Cancer Res. 2020;26:2163–75.PubMedPubMedCentralCrossRef
99.
Pape E, Desmedt E, Zairi F, et al. Leptomeningeal metastasis in melanoma: a prospective clinical study of nine patients. In Vivo. 2012;26:1079–86.PubMed
100.
Glitza IC, Rohlfs M, Guha-Thakurta N, et al. Retrospective review of metastatic melanoma patients with leptomeningeal disease treated with intrathecal interleukin-2. ESMO Open. 2018;3:e000283.PubMedPubMedCentralCrossRef
101.
Arasaratnam M, Hong A, Shivalingam B, et al. Leptomeningeal melanoma: a case series in the era of modern systemic therapy. Pigment Cell Melanoma Res. 2018;31:120–4.PubMedCrossRef
102.
Chorti E, Kebir S, Ahmed MS, et al. Leptomeningeal disease from melanoma: poor prognosis despite new therapeutic modalities. Eur J Cancer. 2021;148:395–404.PubMedCrossRef
103.
Tetu P, Sirven-Villaros L, Cuzzubbo S, et al. Impact of new systemic treatment and radiotherapy in melanoma patients with leptomeningeal metastases. Cancers (Basel). 2020;12:2635.PubMedCentralCrossRef
104.
Glitza IC, Phillips S, Brown C, et al. Single-center phase I/Ib study of concurrent intrathecal and intravenous nivolumab for metastatic melanoma patients with leptomeningeal disease (abstract 10008). ASCO Virtual Scientific Program; 2021.
105.
Gutzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF(V600) mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;395:1835–44.PubMedCrossRef
106.
Nathan P, Dummer R, Long GV, et al. LBA43 Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600-mutant unresectable or metastatic melanoma: results from the randomized part 3 of the phase III COMBI-i trial. European Society Medical Oncology Annual Virtual Meeting; 2020.
107.
Banks PD, Lasocki A, Lau PKH, et al. Bevacizumab as a steroid-sparing agent during immunotherapy for melanoma brain metastases: a case series. Health Sci Rep. 2019;2:e115.PubMedPubMedCentralCrossRef
108.
Glitza IC, Guha-Thakurta N, D’Souza NM, et al. Bevacizumab as an effective treatment for radiation necrosis after radiotherapy for melanoma brain metastases. Melanoma Res. 2017;27:580–4.PubMedCrossRef
109.
Taylor MH, Lee CH, Makker V, et al. Phase IB/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumors. J Clin Oncol. 2020;38:1154–63.PubMedPubMedCentralCrossRef
110.
Arance AM, de la Cruz-Merino L, Petrella TM, et al. Lenvatinib (len) plus pembrolizumab (pembro) for patients (pts) with advanced melanoma and confirmed progression on a PD-1 or PD-L1 inhibitor: updated findings of LEAP-004 (abstract 9504). ASCO Annual Virtual Meeting; 2021.
111.
Lebbe C, Meyer N, Mortier L, et al. Evaluation of two dosing regimens for nivolumab in combination with ipilimumab in patients with advanced melanoma: results from the phase IIIb/IV CheckMate 511 Trial. J Clin Oncol. 2019;37:867–75.PubMedPubMedCentralCrossRef
112.
Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015;314:2535–43.PubMedCrossRef
113.
Hilbers ML, Dimitriou F, Lau P, et al. Real-life data for first-line combination immune-checkpoint inhibition and targeted therapy in patients with melanoma brain metastases. Eur J Cancer. 2021;156:149–63.PubMedCrossRef
114.
Lau P, Feran B, Smith L, et al. Melanoma brain metastases that progress on BRAF-MEK inhibitors demonstrate resistance to ipilimumab-nivolumab that is associated with the Innate PD-1 Resistance Signature (IPRES). J Immunother Cancer. 2021;9:e002995.PubMedPubMedCentralCrossRef
115.
Gardner LJ, Ward M, Andtbacka RHI, et al. Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis. Melanoma Res. 2017;27:477–84.PubMedPubMedCentralCrossRef
116.
Tawbi HA, Forsyth PA, Hodi FS, et al. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol. 2021;22:1692–704.PubMedCrossRef
117.
Vogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO Guideline. J Clin Oncol. 2022;40(5):492–516.PubMedCrossRef
118.
Pomeranz Krummel DA, Nasti TH, Izar B, et al. Impact of sequencing radiation therapy and immune checkpoint inhibitors in the treatment of melanoma brain metastases. Int J Radiat Oncol Biol Phys. 2020;108:157–63.PubMedPubMedCentralCrossRef
119.
Du Four S, Janssen Y, Michotte A, et al. Focal radiation necrosis of the brain in patients with melanoma brain metastases treated with pembrolizumab. Cancer Med. 2018;7:4870–9.PubMedPubMedCentralCrossRef
120.
Ahmed KA, Stallworth DG, Kim Y, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol. 2016;27:434–41.PubMedCrossRef
Metadata
Title
Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents
Author
Stergios J. Moschos
Publication date
09-05-2022
Publisher
Springer International Publishing
Published in
American Journal of Clinical Dermatology / Issue 4/2022
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI
https://doi.org/10.1007/s40257-022-00678-z

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