CNS melanoma

Section editors
	Seema Nagpal, MD Palo Alto, CA		Elizabeth Buchbinder, MD Boston, MA LinkedIn

5 regimens on this page 5 variants on this page

Note: these are CNS-specific regimens, please see the main melanoma page for other regimens.

Guidelines

NCCN

• NCCN Guidelines - Central Nervous System Cancers

All lines of therapy

Dabrafenib monotherapy

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Regimen

FDA-recommended dose

Study	Evidence	Efficacy
Long et al. 2012 (BREAK-MB)	Phase II	ORR: 31-39%

Chemotherapy

• Dabrafenib (Tafinlar) 150 mg PO BID

Given until progression of disease

References

1. BREAK-MB: Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. 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. Epub 2012 Oct 8. link to original article contains verified protocol PubMed

Dabrafenib & Trametinib

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Regimen

FDA-recommended dose

Study	Evidence	Efficacy
Davies et al. 2017 (COMBI-MB)	Phase II	ORR: 44-59%

Chemotherapy

• Dabrafenib (Tafinlar) 150 mg PO BID
• Trametinib (Mekinist) 2 mg PO once per day

Continued until progression

References

1. COMBI-MB: Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Márquez-Rodas I, Del Vecchio M, Lebbé C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. 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 Jul;18(7):863-873. Epub 2017 Jun 4. link to original article contains protocol PubMed

Ipilimumab & Nivolumab

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Regimen

Study	Evidence	Comparator
Long et al. 2018 (ANZMTG 01.14)	Randomized Phase II	Nivolumab

Immunotherapy, part 1

• Ipilimumab (Yervoy) 3 mg/kg IV once on day 1
• Nivolumab (Opdivo) 1 mg/kg IV once on day 1

21-day cycle for 4 cycles, followed by:

Immunotherapy, part 2

• Nivolumab (Opdivo) 3 mg/kg IV over 60 minutes once on day 1

14-day cycles

References

1. ANZMTG 01.14: Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 Mar 27. link to original article contains verified protocol PubMed