Table 2 |.
Predictive biomarkers evaluated in patients with small-cell lung cancer receiving immune-checkpoint inhibitors
| Biomarker | ORR | Median PFS | Median OS |
|---|---|---|---|
| Upfront | |||
| Blood-based TMB | NE | NE | Different blood-based TMB subgroups derive similar levels of benefit from addition of atezolizumab to chemotherapy: ≥10 mut/Mb HR 0.70; >10 mut/Mb HR 0.68; <16 mut/Mb HR 0.71; ≥16 mut/Mb HR 0.63 (REF.3) |
| Tumour or immune cell PD-L1 expression | NE | NE | Patients with PD-L1 <1% derived the highest level of benefit from addition of atezolizumab to chemotherapy (HR 0.51) compared with ≥1% (HR 0.87), <5% (HR 0.77) and ≥5% (HR0.60)34 |
| First-line maintenance | |||
| Tumour PD-L1 expression | Median PFS 11 months among 3 patients with PD-L1-positive tumours who received pembrolizumab9 | NE | NE |
| Tumour–stromal interface PD-L1 expression | ORR 37.5% in 9 patients with PD-L1-positive stroma vs 8.3% in 12 patients with PD-L1-negative stroma receiving pembrolizumab9 | Median PFS 6.5 months in 9 patients with PD-L1-positive stroma vs 1.3 months in 12 patients with PD-L1-negative stroma receiving pembrolizumab9 | Median OS 12.8 months in 9 patients with PD-L1-positive stroma vs 6.5 months in 12 patients with PD-L1-negative stroma receiving pembrolizumab9 |
| CTCs | NE | Not predictive (n = 37)9 | Not predictive (n = 37)9 |
| Second line or later | |||
| Tumour PD-L1 expression | Not predictive5,7 | NE | NE |
| PD-L1 CPS | ORR 35.7% in 42 patients with PD-L1-positive tumours vs 6% in 50 patients with PD-L1-negative tumours receiving pembrolizumab44 | Median PFS 2.1 months in 42 patients with PD-L1-positive tumours vs 1.9 months in 50 patients with PD-L1-negative tumours receiving pembrolizumab | Median OS 14.6 months in 42 patients with PD-L1-positive tumours vs 7.7 months in 50 patients with PD-L1-negative tumours receiving pembrolizumab44 |
| TMB | ORRs 21.3% and 46.2% in patients in the highest TMB tertile receiving nivolumab or ipilimumab plus nivolumab versus 6.8% and 16.0% and 4.8% and 22.2% in the medium and low TMB tertiles, respectively7,48 | Median PFS 1.3, 1.3 and 1.4 months, and 1.5, 1.3 and 7.8 months in the low, medium and high TMB tertiles in response to nivolumab or nivolumab plus ipilimumab, respectively7 | Median OS 3.1, 3.9 and 5.4 months, and 3.4, 3.6 and 22 months in the low, medium and high TMB tertiles in response to nivolumab or nivolumab plus ipilimumab, respectively7 |
| TIL signature | T cell-inflamed GEP associated with superior ORR in patients with solid tumours receiving pembrolizumab including SCLC (P = 0.012)48 | T cell-inflamed GEP associated with longer PFS in patients with solid tumours receiving pembrolizumab including SCLC (P = 0.017)48 | NE |
CPS, combined positive score; CTC, circulating tumour cell; GEP, gene-expression profile; mut/Mb, mutations per megabase; NE, not evaluated; ORR, objective response rate; OS, overall survival; PD-L1, programmed cell death 1 ligand 1; PFS, progression-free survival; SCLC, small-cell lung cancer; TIL, tumour-infiltrating lymphocyte; TMB, tumour mutational burden.