Difference between revisions of "CNS melanoma"
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=Guidelines= | =Guidelines= | ||
==EANO/ESMO== | ==EANO/ESMO== | ||
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*'''2017:''' Le Rhun et al. [https://www.esmo.org/Guidelines/Neuro-Oncology/EANO-ESMO-Leptomeningeal-Metastasis-Clinical-Practice-Guidelines EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours] | *'''2017:''' Le Rhun et al. [https://www.esmo.org/Guidelines/Neuro-Oncology/EANO-ESMO-Leptomeningeal-Metastasis-Clinical-Practice-Guidelines EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours] | ||
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==[https://www.nccn.org/ NCCN]== | ==[https://www.nccn.org/ NCCN]== | ||
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*[https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf NCCN Guidelines - Central Nervous System Cancers] | *[https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf NCCN Guidelines - Central Nervous System Cancers] | ||
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=All lines of therapy= | =All lines of therapy= | ||
==Dabrafenib monotherapy {{#subobject:8f3562|Regimen=1}}== | ==Dabrafenib monotherapy {{#subobject:8f3562|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:fa5aa0|Variant=1}}=== | ===Regimen {{#subobject:fa5aa0|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
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|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
* [[Biomarkers#Genes#BRAF|BRAF]] V600 mutant | * [[Biomarkers#Genes#BRAF|BRAF]] V600 mutant | ||
* Study Inclusion criteria: Val600Glu or Val600Lys | * Study Inclusion criteria: Val600Glu or Val600Lys | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
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*[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day | *[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day | ||
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'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
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#'''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. [https://doi.org/10.1016/S1470-2045(12)70431-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23051966 PubMed] NCT01266967 | #'''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. [https://doi.org/10.1016/S1470-2045(12)70431-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23051966 PubMed] NCT01266967 | ||
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==Dabrafenib & Trametinib {{#subobject:7d3694|Regimen=1}}== | ==Dabrafenib & Trametinib {{#subobject:7d3694|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:23212f|Variant=1}}=== | ===Regimen {{#subobject:23212f|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 81: | Line 75: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
* ''[[Biomarkers#Genes#BRAF|BRAF]]'' V600 mutant | * ''[[Biomarkers#Genes#BRAF|BRAF]]'' V600 mutant | ||
* Clinical Trial Inclusion: BRAF V600 E/K/D/R | * Clinical Trial Inclusion: BRAF V600 E/K/D/R | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day | *[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day | ||
*[[Trametinib (Mekinist)]] 2 mg PO once per day | *[[Trametinib (Mekinist)]] 2 mg PO once per day | ||
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'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
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#'''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. [https://doi.org/10.1016/S1470-2045(17)30429-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28592387 PubMed] NCT02039947 | #'''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. [https://doi.org/10.1016/S1470-2045(17)30429-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28592387 PubMed] NCT02039947 | ||
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==Fotemustine monotherapy {{#subobject:28162f|Regimen=1}}== | ==Fotemustine monotherapy {{#subobject:28162f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:1cb5ae|Variant=1}}=== | ===Regimen {{#subobject:1cb5ae|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fotemustine (Muphoran)]] | *[[Fotemustine (Muphoran)]] | ||
− | === | + | </div></div> |
+ | ===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. [https://journals.lww.com/melanomaresearch/pages/articleviewer.aspx?year=2003&issue=02000&article=00016&type=abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/12569292 PubMed] | # 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. [https://journals.lww.com/melanomaresearch/pages/articleviewer.aspx?year=2003&issue=02000&article=00016&type=abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/12569292 PubMed] | ||
#'''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. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] NCT02460068 | #'''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. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] NCT02460068 | ||
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==Ipilimumab & Nivolumab {{#subobject:28103f|Regimen=1}}== | ==Ipilimumab & Nivolumab {{#subobject:28103f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:6cf5ae|Variant=1}}=== | ===Regimen {{#subobject:6cf5ae|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
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*[[Ipilimumab (Yervoy)]] as follows: | *[[Ipilimumab (Yervoy)]] as follows: | ||
**Cycles 1 to 4: 3 mg/kg IV once on day 1 | **Cycles 1 to 4: 3 mg/kg IV once on day 1 | ||
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**Cycles 1 to 4: 1 mg/kg IV once on day 1 | **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 | **Cycle 5 onwards: 3 mg/kg IV over 60 minutes once on day 1 | ||
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'''21-day cycle for 4 cycles, then 14-day cycles''' | '''21-day cycle for 4 cycles, then 14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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 Mar 27. [https://doi.org/10.1016/S1470-2045(18)30139-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29602646 PubMed] NCT02374242 | #'''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. [https://doi.org/10.1016/S1470-2045(18)30139-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29602646 PubMed] 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. [https://doi.org/10.1056/nejmoa1805453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8011001/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30134131/ PubMed] NCT02320058 | #'''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. [https://doi.org/10.1056/nejmoa1805453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8011001/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30134131/ PubMed] 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. [https://doi.org/10.1093/neuonc/noab094 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8563325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33880555/ PubMed] | ##'''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. [https://doi.org/10.1093/neuonc/noab094 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8563325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33880555/ PubMed] | ||
#'''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. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] NCT02460068 | #'''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. [https://doi.org/10.1158/1078-0432.ccr-21-1046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34112708/ PubMed] NCT02460068 | ||
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==Vemurafenib monotherapy {{#subobject:28825f|Regimen=1}}== | ==Vemurafenib monotherapy {{#subobject:28825f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:6cfyyz|Variant=1}}=== | ===Regimen {{#subobject:6cfyyz|Variant=1}}=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
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|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*[[Biomarkers#Genes#BRAF|BRAFV600]] mutant | *[[Biomarkers#Genes#BRAF|BRAFV600]] mutant | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Vemurafenib (Zelboraf)]] | *[[Vemurafenib (Zelboraf)]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
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#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. [https://doi.org/10.1093/annonc/mdw641 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27993793 PubMed] NCT01378975 | #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. [https://doi.org/10.1093/annonc/mdw641 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27993793 PubMed] NCT01378975 | ||
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[[Category:CNS melanoma regimens]] | [[Category:CNS melanoma regimens]] | ||
− | [[Category: | + | [[Category:Site-specific pages]] |
[[Category:CNS cancers]] | [[Category:CNS cancers]] |
Revision as of 01:40, 29 January 2023
Section editors | |||
---|---|---|---|
Seema Nagpal, MD Stanford University Palo Alto, CA |
Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA |
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
All lines of therapy
Dabrafenib monotherapy
Regimen
FDA-recommended dose |
Study | Years 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
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 contains dosing details in manuscript PubMed NCT01266967
Dabrafenib & Trametinib
Regimen
FDA-recommended dose |
Study | Years 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 contains dosing details in abstract PubMed NCT02039947
Fotemustine monotherapy
Regimen
Study | Years 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 |
2. Ipilimumab & Nivolumab | Inferior OS |
Chemotherapy
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 PubMed
- 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 PubMed NCT02460068
Ipilimumab & Nivolumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Di Giacomo et al. 2021 (NIBIT-M2) | 2013-2018 | Phase 3 (E-esc) | 1. Fotemustine | Superior OS Median OS: 29.2 vs 8.5 mo (HR 0.44, 95% CI 0.22-0.87) |
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 Mar 27. link to original article contains dosing details in manuscript PubMed 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 contains dosing details in manuscript PubMed 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 PubMed
- 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 PubMed NCT02460068
Vemurafenib monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
McArthur et al. 2017 | 2011-2013 | Phase 2 (RT) |
Biomarker eligibility criteria
- BRAFV600 mutant
Targeted therapy
References
- 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 NCT01378975