Chapter 3 90 Results Biomarker characteristics and demographics To evaluate the predictive performance of various biomarker combinations, we first analyzed pretreatment tumor samples from 162 advanced stage NSCLC patients treated with nivolumab. Nine biomarkers were assessed: (1) the total number of CD8 TILs per mm2, (2) the percentage intra-tumoral (IT) CD8 T cells of total CD8 TILs, (3) the number of PD-1T TILs per mm2 (4) the CD3-positive area per mm2 to estimate the presence of CD3 TILs (5) the CD20-positive area per mm2 to estimate the presence of B cells (6) the number of TLS and (7) the combined number of TLS and LA (referred as TLS+LA) per mm2, (8) the PD-L1 Tumor Proportion Score (TPS) and (9) the TIS score (NanoString) (Fig. 1). CD8 TILs and IT-CD8 T cells were successfully assessed in 132/162 (81%), PD-1T TILs in 103/162 (64%), CD3 TILs, CD20+ B cells, TLS and TLS+LA in 128/162 (79%), PD-L1 TPS in 134/162 (83%) and TIS in 68/162 (42%) samples (Table 1, Fig. S1). The use of solely archival samples led to a subset that lacked sufficient tumor tissue, as these samples had been previously used for analyses in the standard diagnostic routine. Additional exclusion criteria for each biomarker are provided in Fig. S1. Patients with results for at least two biomarkers (n=135) were randomly assigned to a training (n=55) and validation (n=80) cohort. This randomization was stratified for clinical benefit to ensure that in both cohorts, 1 in 3 patients reached disease control at 6 months (DC 6m) and 1 in 5 patients reached disease control at 12 months (DC 12m), respectively. Due to the limited availability of patients with TIS scores (n=68), these patients were proportionately distributed in the randomization process (Table 1, Fig. S1). Individual results for each biomarker per patient are detailed in Table S1. No significant differences in demographic characteristics were observed between the training and validation cohorts (Table 2).
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