Home Forums Melanoma Diagnosis: Stage IV Interesting for BRAF negative patients..

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  • #21083
    Catherine Poole
    Keymaster
    #59483
    cltml
    Participant

    Catherine,

    I’m BRAF neg and have always ignored Zelboraf posts. I’m not sure how MEK inhibitors would work for me. Can you explain why this development is important? Thanks.

    cltml

    #59484
    buffcody
    Participant

    As a BRAF negative who is just completing a course of ipi but not tested yet for NRAS, I’m intrigued and heartened by the comment: “Recent data for mutated NRAS as a predictive factor for response to high-dose interleukin 2 reinforces the notion of immunotherapies as front-line treatment for NRAS-mutated metastatic melanoma,” wrote Geoffrey T. Gibney, MD, and Jeffrey S. Weber, MD, of the department of cutaneous oncology and melanoma research, Moffitt Cancer. Anybody know where the “data” are presented or anything more about this?

    #59485
    Catherine Poole
    Keymaster

    My hope for this lies in the fact that almost half our patients are BRAF negative and miss out the bonus of the BRAF therapies. The MEK drug has potential for both NRAS positive and other patients who are BRAF negative. I’m not sure about that connection to IL2 although the statement came from a center that uses that still as a therapy.

    But the good news is the potential for a new therapy for BRAf negative and our scientific board is optimistic about this approach. One drug, MEK 162 will be coming out in trials this spring combined with LGX1818, a BRAF. It is a phase III, so it could move to approval as single agents. The GSK MEK is moving to approval now. We need options and this is a good one.

    #59486
    kylez
    Participant

    UCSF tested me for some NRAS mutations and my tumor had NRAS G12A mutated. So my eyes were drawn to the same passage in the article. I’ve been stable with disease control for awhile now, after IL-2 followed 9 months later by IPI.

    – Kyle

    #59487
    kylez
    Participant

    Buffcody,

    Jim B. on another forum posted this link to a fully published article mentioning the NRAS/immunology possible connection in the context of IL-2:

    http://www.box.net/shared/0awoalt79qysvnn5aiat” class=”bbcode_url”>http://www.box.net/shared/0awoalt79qysvnn5aiat

    The article describes a specific study (see footnote 58) saying, “In this study, the response rate was 47% in patients whose tumors had an NRAS mutation, with a nonstatistically longer progression-free survival and OS versus wildtype patients. These results suggest that the NRAS mutational status could be a possible biomarker for selecting patients with melanoma for IL-2 treatment.”

    The referenced study in footnote 58 is “Joseph RW, Sullivan RJ, Harrell R, Stemke-Hale K, Panka D, Manoukian G, et al. Correlation of NRAS mutations with clinical response to

    high-dose IL-2 in patients with advanced melanoma. J Immunother2012;35:66–72.”

    #59488
    Anonymous
    Guest

    Wow, great read Frank. The pieces to this nightmare puzzle are starting to fit together and form an overall picture. Hope springs forth.

    Jeff

    #59489
    Catherine Poole
    Keymaster

    According to Keith Flaherty, MD of our scientific advisory board: This is data from Harvard and MD Anderson making an initial association between NRAS mutations and higher response to high-dose IL-2. Given the number of patients included in the analysis, the relationship looks potentially real, but definitely needs to be confirmed in an independent group of patients.

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