CNS melanoma

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Note: these are CNS-specific regimens, please see the main melanoma page for other regimens.
Last updated on 2024-07-23:5 regimens on this page
5 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==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 EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Cutaneous Melanoma and NCCN Guidelines - Central Nervous System Cancers.
=All lines of therapy=
==Dabrafenib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Efficacy
Long et al. 2012 (BREAK-MB)	2011 	Phase 2 (RT)	ORR: 31-39%
====Biomarker eligibility criteria====
* BRAF V600 mutant 
* Study Inclusion criteria: Val600Glu or Val600Lys 
====Targeted therapy====
*Dabrafenib (Tafinlar) 150 mg PO twice per day
Continued indefinitely
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01266967
==Dabrafenib & Trametinib==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Efficacy
Davies et al. 2017 (COMBI-MB)	2014-2016 	Phase 2 (RT)	ORR: 44-59%
====Biomarker eligibility criteria====
* BRAF V600 mutant
* Clinical Trial Inclusion: BRAF V600 E/K/D/R 
====Targeted therapy====
*Dabrafenib (Tafinlar) 150 mg PO twice per day
*Trametinib (Mekinist) 2 mg PO once per day
Continued indefinitely
===References===
#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 dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT02039947
==Fotemustine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mornex et al. 2003 	1991-1997 	Phase 3 (C)	Fotemustine & WBRT 	Did not meet endpoint of OS
Di Giacomo et al. 2021 (NIBIT-M2)	2013-2018 	Phase 3 (C)	1. Fotemustine & Ipilimumab	Did not meet primary endpoint of OS
Di Giacomo et al. 2021 (NIBIT-M2)	2013-2018 	Phase 3 (C)	2. Ipilimumab & Nivolumab 	Shorter OS
====Chemotherapy====
*Fotemustine (Muphoran) as follows:
**Cycle 1: 100 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
**Cycles 2 to 7: 100 mg/m2 IV over 60 minutes once on day 1
8-week course, then 21-day cycle for 6 cycles
===References===
# Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay MM, Lesimple T, Tilgen W, Bui BN, Guillot B, Ulrich J, Bourdin S, Mousseau M, Cupissol D, Bonneterre ME, De Gislain C, Bensadoun RJ, Clavel M. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res. 2003 Feb;13(1):97-103. link to original article EuroPMC
#NIBIT-M2: Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02460068
==Ipilimumab & Nivolumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Di Giacomo et al. 2021 (NIBIT-M2)	2013-2018 	Phase 3 (E-esc) 	1. Fotemustine 	Longer OS (primary endpoint)Median OS: 29.2 vs 8.5 mo(HR 0.44, 95% CI 0.22-0.87)
Di Giacomo et al. 2021 (NIBIT-M2)	2013-2018 	Phase 3 (E-esc) 	2. Fotemustine & Ipilimumab	Not reported
Long et al. 2018 (ANZMTG 01.14) 	2014-2017 	Randomized Phase 2 (E-esc)	Nivolumab 	Did not meet primary endpoint of intracranial response from week 12
Tawbi et al. 2018 (CheckMate 204)	2015-2017 	Phase 2 	 	
====Immunotherapy====
*Ipilimumab (Yervoy) as follows:
**Cycles 1 to 4: 3 mg/kg IV once on day 1
*Nivolumab (Opdivo) as follows:
**Cycles 1 to 4: 1 mg/kg IV once on day 1
**Cycle 5 onwards: 3 mg/kg IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 14-day cycles
===References===
#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 May;19(5):672-681. Epub 2018 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02374242
#CheckMate 204: Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23;379(8):722-730. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02320058
##Update: Tawbi HA, Forsyth PA, Hodi FS, Lao CD, Moschos SJ, Hamid O, Atkins MB, Lewis K, Thomas RP, Glaspy JA, Jang S, Algazi AP, Khushalani NI, Postow MA, Pavlick AC, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Tarhini AA, Sumbul A, Rizzo JI, Margolin KA. 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 Nov 2;23(11):1961-1973. link to original article link to PMC article EuroPMC
#NIBIT-M2: Di Giacomo AM, Chiarion-Sileni V, Del Vecchio M, Ferrucci PF, Guida M, Quaglino P, Guidoboni M, Marchetti P, Cutaia O, Amato G, Covre A, Camerini R, Calabrò L, Valente M, Giannarelli D, Mandalà M, Maio M. Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases. Clin Cancer Res. 2021 Sep 1;27(17):4737-4745. Epub 2021 Jun 10. link to original article EuroPMC NCT02460068
==Vemurafenib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
McArthur et al. 2017 (MO25743)	2011-2013 	Phase 2 (RT)
====Biomarker eligibility criteria====
*BRAFV600 mutant
====Targeted therapy====
*Vemurafenib (Zelboraf) 960 mg PO twice per day
Continued indefinitely
===References===
#MO25743: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01378975
Category:CNS melanoma regimens
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Category:CNS cancers