Melanoma, NRAS-mutated

Section editor transclusions 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

Advanced or metastatic disease, TKI-naive

Binimetinib monotherapy

Regimen

Study	Years 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 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

1. 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
2. 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	Years 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

1. 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