CNS melanoma

Section editors
	Seema Nagpal, MD Stanford University Palo Alto, CA		Elizabeth Buchbinder, MD Dana-Farber Cancer Institute 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

EANO/ESMO

• 2017: Le Rhun et al. EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours

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 (RT)	ORR: 31-39%

Biomarker:

• BRAF V600 mutant
• Study Inclusion criteria: Val600Glu or Val600Lys

Chemotherapy

• Dabrafenib (Tafinlar) 150 mg PO twice per day

Continued indefinitely

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%

Biomarkers

• BRAF V600 mutant
• Clinical Trial Inclusion: BRAF V600 E/K/D/R

Chemotherapy

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

Continued indefinitely

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	Comparative Efficacy
Long et al. 2018 (ANZMTG 01.14)	Randomized Phase II (E-esc)	Nivolumab	Did not meet primary endpoint of intracranial response from week 12

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

Vemurafenib monotherapy

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Regimen

Study	Evidence
McArthur et al. 2017	Phase II (RT)

Biomarker

• BRAFV600 mutant

Chemotherapy

• Vemurafenib (Zelboraf)

References

1. McArthur GA, Maio M, Arance A, Nathan P, Blank C, Avril MF, Garbe C, Hauschild A, Schadendorf D, Hamid O, Fluck M, Thebeau M, Schachter J, Kefford R, Chamberlain M, Makrutzki M, Robson S, Gonzalez R, Margolin K. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. 2017 Mar 1;28(3):634-641. link to original article PubMed