P1.01-43 Programmed-Death Ligand 1 Spectrum in a Large Cohort of Genetically Characterized Non-Small Cell Lung Cancer Patients

Programmed-death ligand 1 (PD-L1) expression, assessed by immunohistochemistry (IHC), is used to select patients (pts) for checkpoint inhibitors. However, the pattern of PD-L1 expression across rare oncogenic alterations remains poorly characterized. We aimed to evaluate PD-L1 expression in a large dataset of pts with activating molecular alterations to define the potential responsiveness to immunotherapy. From 2016 to 2018, we prospectively characterized advanced NSCLC pts from a single institution. Tumor Proportion Score (TPS) for PD-L1 protein expression was evaluated by IHC (22C3 clone) using formalin-fixed paraffin-embedded tumor samples and scored into <1% (negative), 1-49% (weakly positive) and ≥50% (high). DNA and RNA were extracted and analysed by Oncomine Solid Tumour panel (22 genes) and a customized nCounter-based panel (ALK, ROS1, RET, NTRK1, METΔ14). Associations between PD-L1 expression and the most prevalent driver alterations were assessed. Smoking habit and its possible relationship with PD-L1 expression was also appraised. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney tests. TPS for PD-L1 expression was available for a total of 140 patients (pts) fully genotyped. The cohort included: 36% women; 89% adenocarcinoma; 87% smokers. TPS for PD-L1 expression was negative (<1%), weak (1-49%) and high (≥50%) in 40%, 35% and 25% of pts, respectively. Actionable drivers were found in 84 pts (60%) being KRAS (n=43.31%) the most commonly detected, followed by EGFR (n=22.16%), BRAF (n=7.5%), METΔ14 (n=8.6%), ALK (n=3.2%) and ERBB2 (n=1, 1%). Thirty (21.4%) [ME1] pts harboured TP53 co-mutations. By comparing all genotyped cohorts, METΔ14 alteration was associated with higher PD-L1 expression levels compared with other subgroups (median TPS 58.62 vs 25.26, p=0.017[ME2] ). In addition, PD-L1 expression was also higher in pts harbouring any TP53 co-mutation than those with any alteration but TP53-WT (median TPS 41.53 vs 21.45, p=0.035). When KRAS-mut, BRAF-mut and EGFR-mut were evaluated separately, PD-L1 expression was higher in TP53 mutated tumors compared to TP53 WT only in BRAF-mut (p=0.028). Finally, no significant differences were found regarding patients’ smoking status (p=0.527). Our results suggest differential expression of PD-L1 based on the presence of MET alterations and TP53 mutations and highlight the need of further characterizing PD-L1 expression across oncogenic alterations.