A PD-1T signature as clinical applicable biomarker in NSCLC 145 4 ◀ Figure 3. PD-1T signature validation for prediction of non-response to PD-1 blockade. (A) PD-1T signature scores in pretreatment samples from patients with disease control at 12 months (DC 12m) (n=6) and patients with progressive disease (PD) (n=36) in the validation set (n=42). The dashed line indicates a cut-off score of 0.35. Medians, interquartile ranges and minimum/maximum shown in boxplots, **P<0.01 by Mann Whitney U-test. (B) Receiver operating characteristic (ROC) curve for predictive value of the PD-1T signature for DC 12m (AUC 0.87; 95% CI: 0.74-0.99) in the validation cohort (n=42). (C) Heatmap showing the expression of the 12-gene PD-1T signature in pretreatment samples from patients with DC 12m (n=6) and patients with PD (n=36) in the validation cohort (n=42) ordered by probability score. Each column represents one patient (blue: PD-1T signature high (score of ≥0.35), light grey: PD-1T signature low (score of <0.35), green: patients with DC 12m, dark grey: patients with PD) and rows display genes. Positive values (red) indicate higher gene expression and negative values (blue) indicate lower gene expression. (D) Progression-free survival (PFS) (median 8.3 months versus 1.8 months, HR 0.36; 95% CI: 0.18-0.69, ***P<0.001) and (E) overall survival (OS) (median 7.0 months versus 5.6 months, HR 0.34; 95% CI: 0.17-0.68, ***P<0.001) of patients with PD-1T signature high (n=6) and PD-1T signature low (n=36) pretreatment samples in the validation set (n=42). Tick marks represent data censored at the last time the patient was known to be alive and without disease progression or death. P-value was determined by log-rank test. Figure 4. Association of PD-L1 with treatment benefit and survival. (A) PD-L1 tumor proportion score (TPS) in pretreatment samples from patients with DC at 12 months (DC 12m) (n=6) and patients with PD (n=34) in the validation cohort (n=40). Mean shown as dashed line, P=0.30 by Mann Whitney U-test. Note that for 2 patients PD-L1 TPS was unknown. (B) Receiver operating characteristic (ROC) curve for predictive value of PD-L1 TPS for DC 12m (AUC 0.63; 95% CI: 0.34-0.91) in the validation cohort (n=40). (C) Progression-free survival (PFS) (median 5.7 months versus 2.3 months, HR 0.77; 95% CI: 0.38-1.54, P=0.47) and (D) overall survival (OS) (median 11.4 months versus 3.0 months, HR 0.40; 95% CI: 0.20-0.81, *P=0.03) of patients with PDL1 TPS ≥50% (n=9) and PD-L1 TPS <50% (n=31) pretreatment samples in the validation cohort (n=40). (E) PFS (median 4.2 months versus 2.1 months, HR 0.87; 95% CI: 0.46-1.63, P=0.65) and (F) OS (median 8.9 months versus 2.5 months, HR 0.56; 95% CI: 0.30-1.07, *P=0.0498) of patients with PD-L1 TPS ≥1% (n=16) and PD-L1 TPS <1% (n=24) pretreatment samples in the validation cohort (n=40). Tick marks represent data censored at the last time the patient was known to be alive and without disease progression or death. P-value was determined by log-rank test. ▶
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