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    Association details:
    Biomarker:NRAS mutation
    Cancer:Melanoma
    Drug:Mektovi (binimetinib) (MEK inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: A2 - Guideline
    New
    Source:
    ESMO.org
    Excerpt:
    In NRAS-mutated melanoma, MEKis have a limited activity, providing improved PFS with an mPFS of 2.8 months for binimetinib compared with 1.5 for dacarbazine…
    Evidence Level:
    Sensitive: B - Late Trials
    New
    Source:
    Lancet Oncol
    Title:

    Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial

    Excerpt:
    Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy.
    DOI:
    https://doi.org/10.1016/S1470-2045(17)30180-8
    Trial ID:
    NCT01763164
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    New
    Source:
    clinicaltrials.gov
    Title:

    A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

    Excerpt:
    ...- BRAF or NRAS mutation in tumor tissue...
    Trial ID:
    NCT01320085
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    New
    Go to data
    Source:
    clinicaltrials.gov
    Title:

    Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma

    Excerpt:
    ...- Presence of NRAS Q61 mutation in tumor tissue prior to randomization as determined by a Novartis designated central laboratory...
    Trial ID:
    NCT01763164
    Less C2 evidence
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Expert Opin Pharmacother
    Title:

    An overview of binimetinib for the treatment of melanoma

    Published date:
    02/26/2020
    Excerpt:
    Single-agent binimetinib almost doubled median progression-free survival when compared to dacarbazine in patients with NRAS-mutated melanoma.
    DOI:
    10.1080/14656566.2020.1729122
    Evidence Level:
    Sensitive: C3 – Early Trials
    New
    Source:
    Lancet Oncol
    Title:

    MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study

    Excerpt:
    Six (20%) of 30 patients with NRAS-mutated melanoma had a partial response (three confirmed) as did eight (20%) of 41 patients with BRAF-mutated melanoma (two confirmed). The most frequent adverse events were acneiform dermatitis (18 [60%] patients with NRAS -mutated melanoma.
    DOI:
    10.1016/S1470-2045(13)70024-X
    Evidence Level:
    Sensitive: D – Preclinical
    New
    Source:
    Cancer Research
    Title:

    PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo

    Excerpt:
    We used human metastatic melanoma cell lines, which were BRAF-mutant (WM3734, 451Lu, A375, SKMel19), NRAS-mutant (SKMel147, WM1346, WM1366, MelJuso)....The MEK inhibitor binimetinib alone inhibited proliferation by 50% to 60% in the BRAF- and NRAS-mutated...
    DOI:
    10.1158/1078-0432.CCR-16-0064
    Evidence Level:
    Sensitive: D – Preclinical
    New
    Source:
    Mol Cancer
    Title:

    MEK targeting in N-RAS mutated metastatic melanoma

    Excerpt:
    All N-RAS mutant melanoma cultures tested in our study (n = 7) were sensitive to MEK inhibition 162. Exposure to MEK162 reduced ERK1/2 phosphorylation, and induced apoptosis. Clonogenic survival was significantly reduced in sensitive melanoma cell cultures.
    DOI:
    10.1186/1476-4598-13-45