mutations detected by tumour next-generation sequencing in non-small cell lung cancer: impact on response to therapy and disease course.

BACKGROUND

Data regarding the prevalence and clinical relevance of mutations in non-small cell lung cancer (NSCLC) is limited. Our objective was to evaluate the impact of pathogenic variants detected by tumour next-generation sequencing (NGS) on disease course and response to therapy.

METHODS

We performed a retrospective analysis of all consecutive NSCLC patients with available NGS reports in a single institution between 01/2015 and 08/2020. Pathogenicity of identified mutations was determined according to American College of Medical Genetics (ACMG) guidelines. Log rank and cox regression analyses were used to determine the association between mutation status, overall survival (OS) and progression-free survival (PFS) under various front-line treatment modalities for advanced disease.

RESULTS

Out of 445 patients with NGS data (54% tissue, 46% liquid), 109 (24.5%) patients had a documented variant; 5.6% (25/445) had a pathogenic/likely pathogenic variant (). Forty percent (10/25) of patients had no co-occurring NSCLC driver mutations. Patients with NSCLC had a less prominent smoking history [mean 42.6 (29.2) 25.7 (24.0) pack years; P=0.024]. Median PFS with first-line chemo-immunotherapy was significantly prolonged for patients (n=7) compared with wild-type () patients (n=30) (HR =0.279; P=0.021, 95% CI: 0.094-0.825).

CONCLUSIONS

-mutated NSCLC can represent a specific subtype of pulmonary carcinoma. Patients whose tumours harbor mutations present with a less prominent smoking history and exhibit prolonged PFS with chemo-immunotherapy combinations compared with controls. In a subset of these patients, is the sole identifiable putative driver mutation, hinting at a significant role for loss in oncogenesis.