# PD-L1 Expression and Comprehensive Genomic Profiling in Advanced NSCLC: A Single-Centre Experience

## TL;DR

This study explores how PD-L1 expression and genetic mutations relate to treatment outcomes in advanced lung cancer patients.

## Contribution

The study identifies specific genetic mutations associated with fast disease progression in NSCLC patients undergoing immunotherapy.

## Key findings

- TP53 mutations are more common in tumors with high PD-L1 and TMB levels.
- STK11 mutations are linked to lower PD-L1 and higher TMB levels.
- KEAP1 mutations are associated with progressive disease in patients treated with immunotherapy.

## Abstract

Although immunotherapy has led to a breakthrough in the treatment of NSCLC, fast disease progression in some patients remains problematic. Great efforts are being made to identify the mechanisms of immune resistance and to establish new predictive and prognostic biomarkers. The aim of this study was to evaluate the association between PD-L1 expression, genetic alterations, and prognosis in patients diagnosed with metastatic NSCLC. PD-L1 expression and genetic profiling using NGS were assessed in 50 patients with advanced NSCLC who were negative for EGFR mutations. According to this study results, positive PD-L1 expression was detected in 62% of cases, whereas high TMB was detected in 34% of cases. Targetable mutations were detected in 33.4% of cases. The TP53 mutation was more likely to be found in tumours with higher PD-L1 and TMB levels (median 45 vs. 0, p = 0.005; median 10 vs. 4.5, p = 0.008, respectively). Meanwhile, STK11 mutation was associated with lower PD-L1 and higher TMB levels (median 0 vs. 17.5, p = 0.019; median 11.5 vs. 6, p = 0.047). Fast disease progression was observed in 22.2% of cases when immunotherapy alone or combined with chemotherapy was administered, with the most frequently detected TP53 (87.5%), STK11 (37.5%), and KEAP1 (37.5%) mutations in this part of the population. Progressive disease was more likely to be found in patients with KEAP1 mutation than in those with wild-type KEAP1 (75% vs. 18.8%, p = 0.02). To conclude, significant associations were found between PD-L1, TMB statuses and mutations in STK11 and TP53. Fast disease progression was established in 1/5 of the entire population treated with immunotherapy or chemo-immunotherapy. TP53, STK11, and KEAP1 mutations were most frequently detected in patients with fast disease progression. The KEAP1 mutation was associated with progressive disease in patients with advanced NSCLC. Our results suggest that a specific genetic profile could serve as a predictor of fast progression in a selected group of patients.