Analysis of the benefit of anti-PD-1 monotherapy according to NGS-diagnosed genetic alterations in patients with non-small cell lung cancer

• Published in: Exploration of targeted anti-tumor therapy 2024-12, Vol.5 (6), p.1435-1449
• Main Authors: De Saint Basile, Hortense, Elaidi, Reza, Maaradji, Zineb, Blons, Hélène, BenDhiab, Rym, Gibault, Laure, Fabre, Elizabeth
• Format: Article
• Language: English
• Subjects: biomarker; checkpoint inhibitors; co-mutations; kras; mutations; ngs; non-small cell lung cancer; tp53
• ISSN: 2692-3114; 2692-3114
• DOI: 10.37349/etat.2024.00283

Aim: Immune checkpoint inhibitors improved the survival of advanced non-small cell lung cancer. However, only 20% of patients respond to these treatments and the search for predictive biomarkers of response is still topical. The objective of this work is to analyze the anti-PD-1 monotherapy benefit based on genetic alterations diagnosed by next generation sequencing (NGS), in advanced non-small cell lung cancer. Methods: Patients with advanced non-small cell lung cancer treated with immunotherapy were retrospectively included in this monocentric study. Clinical data, immunohistochemical expression of PD-L1 and molecular data, with a 22-genes NGS panel, were collected. Results: 107 patients were included. The median age was 65 years [59; 73], 70 were men (65%), 96 had adenocarcinoma (90%), 33 were receiving a first line (31%). 54 patients had KRAS mutation (50%) and 56 had TP53 mutation (52%). The remaining mutations were present in fewer than 10 patients. There was no statistically significant differences in median of progression-free or overall survival based on KRAS-only, TP53-only or KRAS-TP53 mutations co-mutated compared to double wild-type patients (P = 0.46 and P = 0.72 respectively). Conclusions: The search for a predictive composite biomarker remains a major issue in the coming years.