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    Association details:
    Biomarker:TMB-H
    Cancer:Melanoma
    Drug:Tecentriq (atezolizumab) (PD-L1 inhibitor) +
    Zelboraf (vemurafenib) (BRAF inhibitor, BRAF V600E inhibitor) +
    Cotellic (cobimetinib) (MEK1 inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: B - Late Trials
    Source:
    Ann Oncol
    Title:

    Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAF V600 mutation-positive melanoma

    Published date:
    02/04/2022
    Excerpt:
    We report exploratory biomarker analyses to optimize targeting of patients who are more likely to benefit from triplet combination therapy....PFS benefit for atezolizumab versus control was greater in patients with high TMB [≥10 mutations/Mb; hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.52-1.02; P = 0.067] versus low TMB (<10 mutations/Mb; HR 0.92; 95% CI 0.65-1.30; P = 0.64)...In patients with elevated LDH, PFS benefit for atezolizumab versus control was greater in the PD-L1- subgroup (HR 0.53; 95% CI 0.29-0.95; P = 0.032) than in the PD-L1+ subgroup (HR 1.16; 95% CI 0.75-1.80; P = 0.51).
    DOI:
    10.1016/j.annonc.2022.01.076
    Evidence Level:
    Sensitive: B - Late Trials
    Source:
    SITC 2020
    Title:

    307 Atezolizumab plus vemurafenib and cobimetinib provides favorable survival outcomes in patients with high tumor mutation burden and proinflammatory gene signature in the phase 3 IMspire150 study

    Published date:
    11/09/2020
    Excerpt:
    ...the magnitude of the PFS benefit with A+V+C vs P+V+C was markedly higher in patients with high TMB (≥10 mutations/Mb) compared with patients with low TMB (<10 mutations/Mb) in whom the benefit between treatment arms was comparable...
    DOI:
    http://dx.doi.org/10.1136/jitc-2020-SITC2020.0307