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Data on BRAF/Mek before Nivo/Ipi?

Forums General Melanoma Community Data on BRAF/Mek before Nivo/Ipi?

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      Curious if there’s any data on the efficacy of doing BRAF/Mek before Nivo/Ipi.  I found a study comparing the 2 as front line therapies but not the efficacy of doing one before the other.
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          Perhaps these reports will interest you:
          <h3 class=”post-title entry-title”>ASCO 2018 – Optimal sequencing of anti-PD-1 and BRAFi in Stage III patients –</h3>
          Within this report – – there is this:
          <p style=”font-weight: 400;”><u>First-line immunotherapy versus targeted therapy in patients with BRAF-mutant advanced melanoma: a real-world analysis.</u>  Pavlick, Zhao, Lee, et al.  Future Oncol. Feb 2021.</p>
          <p style=”font-weight: 400;”>Aim: To compare effectiveness of nivolumab + ipilimumab (NIVO + IPI) versus BRAF + MEK inhibitors (BRAFi + MEKi) in patients with BRAF-mutant advanced melanoma in the real-world setting. </p>
          <p style=”font-weight: 400;”>Materials & methods: This study used the Flatiron Health electronic medical record database. Results: After adjusting for differences in baseline characteristics, NIVO + IPI was associated with a 32% reduction in risk of death versus BRAFi + MEKi. At a mean follow-up of 15-16 months, 64% of NIVO + IPI patients and 43% of BRAFi + MEKi patients were alive; subsequent therapy was administered to 33 and 41% of patients, respectively. After first-line NIVO + IPI, 20% of patients died before subsequent therapy, whereas 32% died after first-line BRAFi + MEKi.</p>
          <p style=”font-weight: 400;”>Conclusion: In this real-world study, patients treated with first-line NIVO + IPI showed significant survival benefit versus those receiving first-line BRAFi + MEKi.</p>
          There is also this:
          <h3 class=”post-title entry-title”>Melanoma patients want to know! What do I choose? Targeted or immunotherapy? What happens then? –</h3>
          There is this:
          <h3 class=”post-title entry-title”>Results for Stage III melanoma peeps who recurred after adjuvant targeted therapy –</h3>
          Some of these are, as you found, more a comparison of targeted vs immunotherapy rather than a study of the sequential use.  However, there are some data specific to that point here.  We do know that immunotherapy works best with the lowest possible tumor burden for most, so a plan utilizing targeted therapy to quickly decrease that burden in BRAF positive melanoma patients, then rapidly switching to immunotherapy before resistance develops, has been used to good effect in many.   Studies often note, when looking at responses to immunotherapy, that “treatment naive” patients do best. However, most of the time that is referring to those who have not experienced prior immunotherapy. When those studies are simply referring to patients who have had multiple lines of prior treatments doing less well, I am not sure we can attribute the difficulty of bringing the disease under control to the effects of the prior treatment.  Instead, it may simply be that for those in that unfortunate position, their melanoma, or their response to melanoma, is just far more difficult to manage than it is for others.

          Hope this helps.  Feel free to use the search bubble on my blog for more reports if you like.  celeste

          ed williams
            Recent article with Dr. Long of Australia as one of the authors looked at human data and mouse experiments and the early findings (require more human experimentation) but suggest targeted therapy resistance effects immunotherapy performance. I will let you read what they have found and their observations!
              Thanks Bubbles and Ed.
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