Onkologie. 2021:15(4):164-168 | DOI: 10.36290/xon.2021.032

Advances in the systemic treatment of brain metastases in malignant melanoma

Radek Lakomý1, Alexandr Poprach1, Tomáš Kazda2
1 Klinika komplexní onkologické péče, Masarykův onkologický ústav a LF MU, Brno
2 Klinika radiační onkologie, Masarykův onkologický ústav a LF MU, Brno

Brain metastases are a significant negative prognostic factor, not only in malignant melanoma. With the development and availability of imaging methods, with progress in the field of neurosurgery, radiotherapy and especially with the advent of modern systemic treatment, the survival of these patients is significantly improving. The treatment of brain metastases requires a multidisciplinary approach. In a limited number of metastases, the treatment is based on neurosurgery and/or radiosurgery. We often combine the local method with modern systemic treatment based on immunotherapy with checkpoint inhibitors or targeted therapy with BRAF and MEK inhibitors. The best results have been achieved with the combination of immunotherapy (nivolumab and ipilimumab) in patients with asymptomatic brain metastases, although with significant immune-related toxicity. Patients with symptomatic brain metastases are still problematic to treat effectively. A combination of targeted therapy and immunotherapy could improve their outcomes. However, knowledge from research into the tumor microenvironment in the brain will be crucial to help us overcome primary and secondary drug resistance.

Keywords: melanoma, brain metastases, neurosurgery, radiotherapy, targeted therapy, immunotherapy.

Published: September 1, 2021  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Lakomý R, Poprach A, Kazda T. Advances in the systemic treatment of brain metastases in malignant melanoma. Onkologie. 2021;15(4):164-168. doi: 10.36290/xon.2021.032.
Download citation

References

  1. Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. 1996 Jul; 7(3): 337-44. Go to original source... Go to PubMed...
  2. Cagney DN, Martin AM, Catalano PJ, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro Oncol. 2017; 19(11): 1511-1521. Go to original source... Go to PubMed...
  3. Becco P, Gallo S, Poletto S, et al. Melanoma Brain Metastases in the Era of Target Therapies: An Overview. Cancers (Basel). 2020 Jun 21; 12(6): 1640. Go to original source... Go to PubMed...
  4. Davies MA, Liu P, McIntyre S, et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011 Apr 15; 117(8): 1687-96. Go to original source... Go to PubMed...
  5. 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 Jun 1; 22(11): 2101-7. Go to original source... Go to PubMed...
  6. 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(8): 1040-1048. Go to original source... Go to PubMed...
  7. 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(8): 1049-1060. Go to original source... Go to PubMed...
  8. Keilholz U, Ascierto PA, Dummer R, et al. ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee. Ann Oncol. 2020 Nov; 31(11): 1435-1448. Go to original source... Go to PubMed...
  9. Garbe C, Amaral T, Peris K, et al. European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2019. Eur J Cancer. 2020 Feb; 126: 159-177. Go to original source... Go to PubMed...
  10. Brown PD, Gondi V, Pugh S, et al. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1; 38(10): 1019-1029. Go to original source... Go to PubMed...
  11. 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 May; 13(5): 459-65. Go to original source... Go to PubMed...
  12. Long GV, Atkinson V, Lo S, Sandhu S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May; 19(5): 672-681. Go to original source... Go to PubMed...
  13. Long VGA GV, Lo S, Sandhu SK, et al. Long-term Outcomes from the Randomized Ph 2 Study of Nivolumab or Nivo+Ipilimumab in Patients with Melanoma Brain Metastases - The ABC trial. Ann Oncol 2019; 30: v533-63. Go to original source...
  14. Tawbi HA, Forsyth PA, Algazi A, et al. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23; 379(8): 722-730. Go to original source... Go to PubMed...
  15. Tawbi HA, Forsyth PA, Hodi FS, 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. 2019; 37(15_suppl): 9501-9501. Go to original source...
  16. Di Giacomo AM, Chiarion Sileni V, Del Vecchio M, et al. Efficacy of ipilimumab plus nivolumab or ipilimumab plus fotemustine vs fotemustine in patients with melanoma metastatic to the brain: Primary analysis of the phase III NIBIT-M2 trial. Ann. Oncol 2020 Sep; 31(suppl_4): S672-S710. Go to original source...
  17. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2; 373(1): 23-34. Erratum in: N Engl J Med. 2018 Nov 29; 379(22): 2185. Go to original source... Go to PubMed...
  18. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-1356. Erratum in: N Engl J Med. 2018 Nov 29; 379(22): 2185. Go to original source... Go to PubMed...
  19. 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 Nov; 13(11): 1087-95. Go to original source... Go to PubMed...
  20. 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 Jul; 18(7): 863-873. Go to original source... Go to PubMed...
  21. Lehrer EJ, Peterson J, Brown PD, et al. Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data. Radiother Oncol. 2019 Jan; 130: 104-112. Go to original source... Go to PubMed...




Oncology

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.