Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma

bMSAF is a prognostic predictor for advanced hepatocellular carcinoma patients treated with immune checkpoint inhibitor camrelizumab and anti‐angiogenic agent apatinib combination therapy

“…Analyses of tissue‐based biomarkers exhibited that tissue‐based tumour mutation burden (tTMB) (optimal cutoff = 52, Supplementary Figure S1A–D ) and tumour neoantigen burden (TNB) (optimal cutoff = 26, Supplementary Table S5 , Supplementary Figure S2A–D ) were not apparent association with response rate or survival benefit in the camrelizumab + apatinib, in which patients with high tTMB showed a non‐significant trend of longer PFS ( p = .063) compared with those with low. This was consistent with previous study, 5 suggesting that there may be no relationship between CD8 + T cell levels and neoantigen load in HCC. 6 Besides, PD‐L1 status was not significantly associated with survival or clinical efficacy in 54 HCC tissues (Supplementary Figure S3A–C ).…”

Immunotherapy biomarkers for HCC: contemporary challenges and emerging opportunities

“…The phase 1b study of atezolizumab plus bevacizumab also found PD-L1 expression on tumor and tumorinfiltrating immune cells to poorly predict progression-free survival [5] . Furthermore, exploratory analyses conducted using archival specimens from this and another early phase trial of atezolizumab plus bevaciumab did not associate tumor mutation burden (TMB) with treatment response or progression-free survival, although high expression of VEGF receptor 2, a T-regulatory signature, and a myeloid inflammation signature were associated with benefit from atezolizumab plus bevacizumab compared with atezolizumab alone [6] . In a more recent extensive biomarker analysis for the IMbrave150 trial, high expression of CD274 and intra-tumor CD8(+) cells density was associated with prolonged patient survival, while high Treg:Teff ratio and expression of HCC tumor markers, such as GPC3 and AFP, were associated with poor outcome [7] .…”

Current and emerging anti-angiogenic therapies in gastrointestinal and hepatobiliary cancers

“…More recently, an integrated molecular analysis was performed, comprising RNA sequencing, DNA sequencing and simple and multiplex immunohistochemistry of 358 patients included in the phase Ib GO30140 ( 144 ) and the phase III IMbrave150 trial ( 114 , 116 ). This showed that pre-existing immunity, including the expression of a T effector transcriptomic signature and CD8+ T cell infiltration, predicted response to the combination of atezolizumab-bevacizumab, but not to sorafenib ( 145 ). Importantly, improved outcomes for the combination vs atezolizumab monotherapy was associated with high VEGFR-2 expression.…”

“…Importantly, improved outcomes for the combination vs atezolizumab monotherapy was associated with high VEGFR-2 expression. Conversely, reduced benefit from the combination was associated with a low Treg/effector T cell ratio ( 145 ). These data highlight the synergistic effects of the combination of atezolizumab-bevacizumab and suggest several predictive biomarkers that will need validation in future trials.…”