Single-center experience using reflex-targeted next-generation sequencing at diagnosis of squamous cell lung carcinoma in daily practice

Abstract

Patients with lung squamous cell carcinoma (LSCC) rarely benefit from targeted therapies in daily practice. Current and future clinical trials targeting genomic alterations may open up promising therapeutic strategies for this population. We evaluated the usefulness and the clinical added value in the real world of the analysis of LSCC at diagnosis using reflex-targeted next-generation sequencing (NGS) on-site in a single hospital center. Targeted DNA and RNA NGS and diagnostic immunohistochemistry for PD-L1 and c-MET were performed on a consecutive series of 108 LSCC patients. The main genomic alterations included mutations in TP53 [56/102; (51.9%)], PIK3CA [9/108; (8.3%)], PTEN [(8/108 (7.4%)], and KRAS [6/108; (5.6%)]. The genes with the most frequent copy number variants (CNV) were PIK3CA CNV [13/108, (12.0%)], EGFR CNV [7/108, (6.5%)], and FGFR CNV [(7/108, (6.5%)]. The expression of PD-L1 (> 1% in 69% of cases) and c-MET (H-score > 150 in 18% of cases) was independent of the genomic alterations. Rare alterations that can be targeted by tyrosine kinase inhibitors (TKI) were detected in four patients, including EGFR p.Asn771_His773dup, EGFR p.Leu861Gln, KRAS p.Gly12Cys, and MET exon 14 skipping. This study demonstrated the potential clinical utility of developing on-site targeted NGS as reflex testing for LSCC to detect molecular targets for personalised treatment using available drugs or for clinical trials. However, none of the patients in our series received targeted therapy. Most of them were treated with chemotherapy or immuno-chemotherapy according to the PD-L1 status and current standard therapeutic guidelines.

Keywords: C-MET; Lung squamous cell carcinoma; Next-generation sequencing; PD-L1; Targeted therapy.