CNS melanoma
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| 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
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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 contains dosing details in manuscript 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 contains dosing details in abstract 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 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 | 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