Chapter 4 142 Table 2. Predictive accuracy of the PD-1T signature and PD-L1 TPS, summary of training and validation results. Biomarker AUC Training cohort (n=41) PD-1T signature 0.97 95% CI: 0.93-1.00 Validation cohort (n=42) PD-1T signature 0.87 95% CI: 0.74-0.99 Validation cohort (n=40) % PD-L1 TPS 0.63 95% CI: 0.34-0.91 Comparison to PD-L1 IHC and PDCD1 gene expression In previous work we showed that the predictive performance of PD-1T TILs was superior to the PD-L1 tumor proportion score (TPS)7. Therefore, we compared the predictive performance of PD-L1 TPS to the PD-1T signature in the validation cohort. 9/42 (21%) pretreatment samples showed a PD-L1 TPS of ≥50%, 7/42 (17%) between 1% and 50% and 24/42 (57%) showed no PD-L1 expression. In 2/42 (5%) the PD-L1 status was unknown and these patients were excluded from further analysis (Table S1, S3). PD-L1 TPS was not significantly higher in patients with DC 12m compared to patients with PD (P=0.30) (Fig. 4A). The AUC was substantially lower compared to the PD1T signature (AUC: 0.63; 95% CI: 0.34-0.91, P=0.13), indicating a lower discriminatory ability (Fig. 4B). At 50% cut-off, the sensitivity was also lower (50%), as well as were specificity (82%), PPV (33%) and NPV (90%) (Table 2). Furthermore, we observed that a PD-L1 TPS of ≥50% was not associated with significantly better PFS (HR 0.77; 95% CI: 0.38-1.54, median PFS 5.7 vs 2.3 months), but did show borderline significance for improved OS (HR 0.40; 95% CI: 0.20-0.81, median OS 11.4 vs 3.0 months) (Fig 4C,D). Next, we assessed the predictive accuracy at 1% cut-off, as this cut-off has also been previously studied, though with contradictory results3–5. Here, sensitivity (50%) and NPV (88%) were similar to the performance of 50% PD-L1 TPS, with only a slightly lower specificity (62%) and PPV (19%) (Table 2). PD-L1 TPS ≥1% showed similar survival outcomes as PD-L1 TPS ≥50% (Fig. 4E,F).
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