Table 2.
Review of select biomarker studies and their ability to enrich responding patient populations
| Biomarker | Drug | Disease/setting | Cutoff | Outcome | Comment |
|---|---|---|---|---|---|
| Tumor PD-L1 | Pembrolizumab59 | NSCLC | 1%–24% | OS – 10 mo | Automated IHC assay with antibody 22C3 |
| Mostly second line | 25%–49% | OS – 10 mo | Food and Drug Administration-approved test – positive = TPS 50%+ | ||
| 50%–74% | OS – 16 mo | ||||
| 75%+ | OS – 17 mo | ||||
| Nivolumab60 | NSCLC second line | <5% | OS – 10 mo | IHC assay with antibody 28-8 | |
| (nonsquamous histology) | 5%+ | OS – 19 mo | |||
| Atezolizumab61 | NSCLC | <1% | OS – 13 mo | SP142 assay | |
| Second line | >1% | OS – 16 mo | |||
| >5% | OS – 16 mo | ||||
| >50% | OS – 21 mo | ||||
| Nivolumab62 | Melanoma | <5% | PFS – 5 mo | IHC assay with antibody 28-8 | |
| First line | >5% | PFS – 22 mo | From pooled analysis | ||
| Pembrolizumab63 | Melanoma | <1% | PFS – 3 mo | IHC assay with antibody 22C3 | |
| Prior treatment | 1%+ | PFS – 12 mo | |||
| Inflammatory gene | Pembrolizumab64 | Head and neck cancer | Positive predictive value | 40% | Interferon gamma genes: CXCL9, CXCL10 |
| Signature | Second line | Negative predictive value | 95% | IDO1, INF gamma, HLA-DRA, and STAT1 | |
| Atezolizumab65 | NSCLC | Teff/INF high | OS – NR median follow-up ~15 mo | Teff/INF gamma gene signature | |
| Second line | Teff/INF low | OS ~10 mo | Determined by gene expression of CD8A GZMA, GZMB, INF gamma, EOMES, CXCL9 CXCL10 and TBX21 | ||
| Mutational burden | Pembrolizumab66 | NSCLC | High (above median) | ORR – 59% | Nonsynonymous |
| Prior treatment | Low (below median) | ORR – 12 | Exom sequencing with 9049 nonsynonymous, coding point mutations considered | ||
| Pembrolizumab66 | NSCLC | High (above median) | PFS – 14.5 mo | Total exonic mutations | |
| Prior treatment | Low (below median) | PFS – 4.1 mo | |||
| Pembrolizumab24 | Colorectal cancer | Mismatch repair deficient | ORR – 40% | Microsatellite instability analysis using an assay from Promega | |
| Second line | Mismatch repair proficient | ORR – 0% | |||
| Angiopoietin 2 | PD-1 inhibitor25 | Melanoma | Low baseline with small increase w/tx | OS =34.6 mo | Serum-based assay |
| Second line | High baseline with high increase w/tx | OS =7.9 mo | Monitored serially – association with vascular endothelial growth factor |
Abbreviations: INF, interferon; IHC, immunohistochemistry; mo, months; NSCLC, non-small-cell lung cancer; OS, overall survival; PD-1, programmed cell death-1; PD-L1, programmed death-ligand 1; PFS, progression-free survival.