Latest revision as of 11:26, 13 May 2024

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	Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL, USA LinkedIn		Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA, USA LinkedIn

Note: these are regimens tested in biomarker-specific populations, please see the main melanoma page for other regimens.

2 regimens on this page 2 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.

NCCN

NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Melanoma: Cutaneous.

Advanced or metastatic disease, TKI-naive

Binimetinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ascierto et al. 2013 (CMEK162X2201)	2011-2012	Phase 2
Dummer et al. 2017 (NEMO)	2013-2015	Phase 3 (E-switch-ooc)	Dacarbazine	Superior PFS (primary endpoint) Median PFS: 2.8 vs 1.5 mo (HR 0.62, 95% CI 0.47-0.80)

Note: dosing is different for BRAF mutations (45 to 60 mg twice per day)

Biomarker eligibility criteria

Gene: NRAS or BRAF
Alteration: mutation [Val600 BRAF]

Targeted therapy

Binimetinib (Mektovi) 45 mg PO twice per day

References

CMEK162X2201: Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013 Mar;14(3):249-56. Epub 2013 Feb 13. link to original article contains dosing details in abstract PubMed NCT01320085
NEMO: Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. Epub 2017 Mar 8. link to original article contains dosing details in abstract PubMed NCT01763164

Dacarbazine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dummer et al. 2017 (NEMO)	2013-2015	Phase 3 (C)	Binimetinib	Inferior PFS

Chemotherapy

Dacarbazine (DTIC) 1000 mg/m² IV once on day 1

21-day cycles

References

NEMO: Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. Epub 2017 Mar 8. link to original article contains dosing details in abstract PubMed NCT01763164

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-|-
+[[#top|Back to Top]]
-|style="background-color:#F0F0F0|[[File:Bethbuchbinder.jpg|frameless|upright=0.3|center]]
+</div>
-|<big>[[User:Bethbuchbinder|Elizabeth Buchbinder, MD]]<br>Dana-Farber Cancer Institute<br>Boston, MA</big><br>[https://www.linkedin.com/in/beth-buchbinder-2a9b994/ LinkedIn]
+{{#lst:Editorial board transclusions|mel}}
-|-
-|}
 <big>'''Note: these are regimens tested in biomarker-specific populations, please see the [[Melanoma|main melanoma page]] for other regimens.'''</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
@@ Line 13: / Line 11: @@
 |}
 {{TOC limit|limit=3}}
+=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.'''
+==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 - Melanoma: Cutaneous].''
 =Advanced or metastatic disease, TKI-naive=
 ==Binimetinib monotherapy {{#subobject:aa3a2b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:8d6382|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 20%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Dates of enrollment
-!style="width: 25%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70024-X/fulltext Ascierto et al. 2013]
+|[https://doi.org/10.1016/S1470-2045(13)70024-X Ascierto et al. 2013 (CMEK162X2201)]
-| style="background-color:#91cf61" |Phase II
+|2011-2012
+| style="background-color:#91cf61" |Phase 2
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30180-8/fulltext Dummer et al. 2017 (NEMO)]
+|[https://doi.org/10.1016/S1470-2045(17)30180-8 Dummer et al. 2017 (NEMO)]
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+|2013-2015
-|[[Melanoma#Dacarbazine_monotherapy|Dacarbazine]]
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|style="background-color:#1a9850"|Superior PFS
+|[[#Dacarbazine_monotherapy|Dacarbazine]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 2.8 vs 1.5 mo<br>(HR 0.62, 95% CI 0.47-0.80)
 |-
 |}
-====Chemotherapy====
+''Note: dosing is different for BRAF mutations (45 to 60 mg twice per day)''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*Gene: NRAS or BRAF
+*Alteration: mutation [Val600 BRAF]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
 *[[Binimetinib (Mektovi)]] 45 mg PO twice per day
+</div></div>
+===References===
+#'''CMEK162X2201:''' Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013 Mar;14(3):249-56. Epub 2013 Feb 13. [https://doi.org/10.1016/S1470-2045(13)70024-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23414587/ PubMed] [https://clinicaltrials.gov/study/NCT01320085 NCT01320085]
+#'''NEMO:''' Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. Epub 2017 Mar 8. [https://doi.org/10.1016/S1470-2045(17)30180-8 link to original article] '''contains dosing details in abstract'''  [https://pubmed.ncbi.nlm.nih.gov/28284557/ PubMed] [https://clinicaltrials.gov/study/NCT01763164 NCT01763164]
-'''Continued indefinitely'''
+==Dacarbazine monotherapy {{#subobject:d3599b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:bede4c|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/10.1016/S1470-2045(17)30180-8 Dummer et al. 2017 (NEMO)]
+|2013-2015
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Binimetinib_monotherapy|Binimetinib]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycles'''
+</div></div>
 ===References===
-# Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013 Mar;14(3):249-56. Epub 2013 Feb 13. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70024-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23414587 PubMed]
+#'''NEMO:''' Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. Epub 2017 Mar 8. [https://doi.org/10.1016/S1470-2045(17)30180-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28284557/ PubMed] [https://clinicaltrials.gov/study/NCT01763164 NCT01763164]
-# '''NEMO:''' Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. Epub 2017 Mar 8. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30180-8/fulltext link to original article] '''contains protocol'''  [https://www.ncbi.nlm.nih.gov/pubmed/28284557 PubMed]
 [[Category:Melanoma regimens]]
 [[Category:Biomarker-specific pages]]
 [[Category:Skin cancers]]

Difference between revisions of "Melanoma, NRAS-mutated"

Latest revision as of 11:26, 13 May 2024

Contents

Guidelines

NCCN

Advanced or metastatic disease, TKI-naive

Binimetinib monotherapy

Regimen

Biomarker eligibility criteria

Targeted therapy

References

Dacarbazine monotherapy

Regimen

Chemotherapy

References

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