Evaluation of PD-L1 Expression and Anti-EGFR Therapy in EGFR-Mutant Non-Small-Cell Lung Cancer

<i>Background and Objectives</i>: Non-small-cell lung cancer (NSCLC) often has epidermal growth factor receptor (<i>EGFR</i>) mutations, which are key targets for therapy. <i>EGFR</i> mutation subtypes, especially exon 19 deletions and exon 21 L858R mutations, influence responses to <i>EGFR</i> tyrosine kinase inhibitors (TKIs) and patient survival. Despite progress in TKI treatments, resistance and different responses remain challenges. This study explores the relationship between <i>EGFR</i> mutation subtypes, PD-L1 expression, and patient outcomes after anti-<i>EGFR</i> therapy. <i>Materials and Methods</i>: We studied 176 cases of <i>EGFR</i> mutation-positive NSCLC. Next-generation sequencing was used to analyze <i>EGFR</i> and other mutations, while PD-L1 expression was evaluated through immunohistochemistry. We analyzed <i>EGFR</i> mutation subtypes, PD-L1 status, treatments, and survival outcomes. <i>Results</i>: Among 176 cases, 88.6% were adenocarcinomas. Within the <i>EGFR</i> mutation spectrum, exon 19 deletions were the most common subtype, accounting for 40.9% of cases, followed by the point mutation in exon 21, which occurred in 35.8% of cases. Less frequent alterations, making up 23.3% of all detected mutations, included mutations in exon 18, insertions, and point mutations such as S768I and T790M in exon 20, as well as changes in exon 2, exon 7, and other less frequently affected regions. Exon 19 mutations were associated with older age, female sex, adenocarcinoma, and bone metastasis (<i>p</i> < 0.05). <i>TP53</i> was the most common concurrent mutation (44.3%). PD-L1 positivity (TPS ≥ 1%) was observed in 48.3%, with high expression (TPS ≥ 50%) in 25.9%. Exon 21 mutations were significantly linked to PD-L1 negativity (<i>p</i> = 0.008). The median overall survival was longest with TKI therapy (51 months), and this was also observed in PD-L1-positive patients, although the difference was not statistically significant. The median progression-free survival for patients treated with TKIs and those with <i>EGFR</i> mutations was 14 months. PD-L1-positive patients receiving TKIs had significantly longer survival than those who did not (51 vs. 17 months, <i>p</i> = 0.003). <i>Conclusions</i>: <i>EGFR</i> mutation subtypes and PD-L1 expression seem to affect treatment outcomes and survival in NSCLC. The observed links emphasize the potential value of combining molecular and immunological markers to guide therapy choices.