Difference between revisions of "CNS melanoma"
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | ||
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− | + | '''Note: these are CNS-specific regimens, please see the [[Melanoma|main melanoma page]] for other regimens.''' | |
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Guidelines= | =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== | ==EANO/ESMO== | ||
− | *'''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] [https://pubmed.ncbi.nlm.nih.gov/28881917 PubMed] |
− | ==[https://www.nccn.org/ NCCN] | + | |
− | + | ==NCCN== | |
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1492 NCCN Guidelines - Cutaneous Melanoma] and [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425 NCCN Guidelines - Central Nervous System Cancers].'' | ||
=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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|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
− | !style="width: | + | !style="width: 25%"|Study |
− | !style="width: | + | !style="width: 25%"|Dates of enrollment |
− | !style="width: | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70431-X Long et al. 2012 (BREAK-MB)] |
− | |style="background-color:#91cf61"|Phase | + | |2011 |
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
| style="background-color:#8c6bb1" |ORR: 31-39% | | style="background-color:#8c6bb1" |ORR: 31-39% | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | *[[Dabrafenib (Tafinlar)]] 150 mg PO | + | ====Biomarker eligibility criteria==== |
− | + | * [[Biomarkers#Genes#BRAF|BRAF]] V600 mutant | |
− | ''' | + | * Study Inclusion criteria: Val600Glu or Val600Lys |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
===References=== | ===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. [https:// | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23051966/ PubMed] [https://clinicaltrials.gov/study/NCT01266967 NCT01266967] |
− | |||
==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" | ||
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|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
− | !style="width: | + | !style="width: 25%"|Study |
− | !style="width: | + | !style="width: 25%"|Dates of enrollment |
− | !style="width: | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5991615/ Davies et al. 2017 (COMBI-MB)] |
− | |style="background-color:#91cf61"|Phase | + | |2014-2016 |
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
| style="background-color:#9ebcda" |ORR: 44-59% | | style="background-color:#9ebcda" |ORR: 44-59% | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | *[[Dabrafenib (Tafinlar)]] 150 mg PO | + | ====Biomarker eligibility criteria==== |
+ | * ''[[Biomarkers#Genes#BRAF|BRAF]]'' V600 mutant | ||
+ | * Clinical Trial Inclusion: BRAF V600 E/K/D/R | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day | ||
*[[Trametinib (Mekinist)]] 2 mg PO once per day | *[[Trametinib (Mekinist)]] 2 mg PO once per day | ||
− | + | '''Continued indefinitely''' | |
− | '''Continued | + | </div></div> |
− | |||
===References=== | ===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. [https:// | + | #'''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] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5991615/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28592387/ PubMed] [https://clinicaltrials.gov/study/NCT02039947 NCT02039947] |
− | == | + | ==Fotemustine monotherapy {{#subobject:28162f|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:1cb5ae|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1097/00008390-200302000-00016 Mornex et al. 2003] | ||
+ | |1991-1997 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Fotemustine_.26_WBRT_999|Fotemustine & WBRT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1158/1078-0432.ccr-21-1046 Di Giacomo et al. 2021 (NIBIT-M2)] | ||
+ | |rowspan=2|2013-2018 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1. [[#Fotemustine_.26_Ipilimumab_999|Fotemustine & Ipilimumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |2. [[#Ipilimumab_.26_Nivolumab|Ipilimumab & Nivolumab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[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://doi.org/10.1097/00008390-200302000-00016 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] [https://clinicaltrials.gov/study/NCT02460068 NCT02460068] | ||
+ | ==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" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 20%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 20%"|Dates of enrollment |
− | !Comparator | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1158/1078-0432.ccr-21-1046 Di Giacomo et al. 2021 (NIBIT-M2)] | ||
+ | |rowspan=2|2013-2018 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1. [[#Fotemustine_monotherapy|Fotemustine]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 29.2 vs 8.5 mo<br>(HR 0.44, 95% CI 0.22-0.87) | ||
+ | |- | ||
+ | |2. [[#Fotemustine_.26_Ipilimumab_999|Fotemustine & Ipilimumab]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(18)30139-6 Long et al. 2018 (ANZMTG 01.14)] | ||
+ | |2014-2017 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | ||
+ | |[[#Nivolumab_monotherapy_999|Nivolumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of intracranial response from week 12 | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8011001/ Tawbi et al. 2018 (CheckMate 204)] |
− | |style="background-color:# | + | |2015-2017 |
− | | | + | | style="background-color:#91cf61" |Phase 2 |
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|} | |} | ||
− | ====Immunotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Ipilimumab (Yervoy)]] 3 mg/kg IV once on day 1 | + | ====Immunotherapy==== |
− | *[[Nivolumab (Opdivo)]] 1 mg/kg IV once on day 1 | + | *[[Ipilimumab (Yervoy)]] as follows: |
− | + | **Cycles 1 to 4: 3 mg/kg IV once on day 1 | |
− | '''21-day cycle for 4 cycles, | + | *[[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''' | |
− | + | </div></div> | |
− | ''' | + | ===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. [https://doi.org/10.1016/S1470-2045(18)30139-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29602646/ PubMed] [https://clinicaltrials.gov/study/NCT02374242 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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30134131/ PubMed] [https://clinicaltrials.gov/study/NCT02320058 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] | ||
+ | #'''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] [https://clinicaltrials.gov/study/NCT02460068 NCT02460068] | ||
+ | ==Vemurafenib monotherapy {{#subobject:28825f|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:6cfyyz|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdw641 McArthur et al. 2017 (MO25743)] | ||
+ | |2011-2013 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *[[Biomarkers#Genes#BRAF|BRAFV600]] mutant | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Vemurafenib (Zelboraf)]] | ||
+ | </div></div> | ||
===References=== | ===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. [https://doi.org/10.1093/annonc/mdw641 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27993793/ PubMed] [https://clinicaltrials.gov/study/NCT01378975 NCT01378975] |
− | |||
[[Category:CNS melanoma regimens]] | [[Category:CNS melanoma regimens]] | ||
− | [[Category: | + | [[Category:Site-specific pages]] |
[[Category:CNS cancers]] | [[Category:CNS cancers]] |
Latest revision as of 23:37, 15 July 2024
Section editor | Section editor | ||
---|---|---|---|
Seema Nagpal, MD Stanford University Palo Alto, CA, USA |
Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA, USA |
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
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 PubMed
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
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 PubMed 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 PubMed 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 |
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 | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Di Giacomo et al. 2021 (NIBIT-M2) | 2013-2018 | Phase 3 (E-esc) | 1. Fotemustine | Superior OS (primary endpoint) 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 May;19(5):672-681. Epub 2018 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 | Dates of enrollment | Evidence |
---|---|---|
McArthur et al. 2017 (MO25743) | 2011-2013 | Phase 2 (RT) |
Biomarker eligibility criteria
- BRAFV600 mutant
Targeted therapy
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 PubMed NCT01378975