Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study

Driver molecular aberrations, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement, play an important role in the oncogenesis and progression of non-squamous non-small-cell lung cancers (NSCLC). Therefore, this study aimed to detect the incidence of driver mutations among non-squamous NSCLC.

This was a retrospective-prospective cohort study on 131 patients with non-squamous NSCLC. Data on age, smoking status, chest symptoms, method of lung cancer diagnosis, molecular testing, including EGFR mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue and serum circulating tumor DNA using next-generation sequencing and ALK gene rearrangement by FFPE tumor tissue, and follow-up data regarding treatment modalities and outcomes were collected.

The median age of the patients was 57 years (range: 32-79 years). Out of 131 patients, 97 were males (74%), and 90 (68.7%) were smokers. Among 128 patients tested, 16 (12.5%) had EGFR mutations detected with either technique by formalin-fixed paraffin-embedded (FFPE) tumor tissue or/and serum circulating tumor DNA using next-generation sequencing, and 6 (4.7%) had ALK rearrangement by FFPE tumor tissue. The majority (62.6%) presented with metastatic disease. Among the 102 patients who received first-line systemic therapy, the objective response rate was 50.0% in mutated NSCLC versus 14.6% in non-mutated (p < 0.001). Among the eight mutated patients who received first-line tyrosine kinase inhibitors (TKIs), 7 patients achieved either complete response or partial response. Among the 22 mutated patients, the median overall survival was 3 months in those who did not receive targeted therapy versus not reached in those who received any type of targeted therapy (p < 0.001).

Screening patients with newly diagnosed non-squamous NSCLC for driver mutations is essential for major prognostic and therapeutic implications. Early administration of TKIs in mutated patients significantly improves disease outcomes.