Table 1.
Overview of the major studies investigating predictive and prognostic biomarkers in neoadjuvant and adjuvant settings.
| Author, year; trial name | Disease stage | Sample size (n) | Setting | Treatment(s) | Biomarker(s) | Results |
|---|---|---|---|---|---|---|
| Tarhini et al., 2009; Intergroup Trial ECOG 1694 [37] | IIB/III | 670 | Adjuvant | HDI | S100B | S100B at baseline and at later time points is a prognostic factor for RFS and OS |
| Weber et al., 2019; CheckMate 238 [66] | IIIB/C–IV | 906 | Adjuvant | Nivolumab vs. ipilimumaba |
IFNγ GES CD8+ T cells in tumor tissue TMB Peripheral blood MDSC |
High TMB, CD8+ T-cell tumor infiltrate and IFNγ expression correlate with better clinical outcomes with nivolumab and ipilimumab A trend towards better RFS in patients with low MDSC levels treated with nivolumab |
| Ascierto et al., 2020; BRIM8 [68] | IIC–IIIC | 498 | Adjuvant | Vemurafenib |
CD8+ T cells and PD-L1 expression in tumor tissue |
High levels of CD8+ T-cell infiltrate and PD-L1+ cells in the TME correlate with better DFS |
| Dummer et al., 2020; COMBI-AD [69] | III | 870 | Adjuvant | Dabrafenib + trametinib |
TMB IFNγ GES |
Low TMB and high IFNγ expression correlate with long-term RFS |
| Amaria et al., 2018 [27] | III | 23 | Neoadjuvant | Nivolumab ± ipilimumaba |
TMB T-cell infiltrate PD-L1 Lymphoid markers |
Baseline and early on-treatment high TMB, CD8+ T-cell infiltrate, PD-L1 and lymphoid marker expression correlate with response |
| Blank et al., 2018; OpACIN [23] | III | 20 | Neoadjuvant | Nivolumab + ipilimumaba |
IFNγ GES Tumor resident T-cell clones CD3, β2M, PD-L1 |
Reduced T-cell infiltrate, low CD3, β2M and PD-L1 expression, and low IFNγ signature correlate with disease relapse |
| Rozeman et al., 2021; OpACIN-neo [25] | III | 86 | Neoadjuvant | Nivolumab + ipilimumaba |
TMB IFNγ GES |
High TMB and IFNγ signature correlate with pCR and low risk of disease relapse |
β2M β2-microglobulin, DFS disease-free survival, GES gene expression signature, HDI high-dose interferon, IFNγ interferon gamma, MDSC myeloid-derived suppressor cells, OS overall survival, pCR pathologic complete response, PD-L1 programmed cell death ligand 1, RFS relapse-free survival, TMB tumor mutational burden, TME tumor microenvironment
aDetails on drug schedules and dosage are provided in the main text