The following is a summary of “Programmed Death-Ligand 1 Copy Number Alteration as an Adjunct Biomarker of Response to Immunotherapy in Advanced NSCLC,” published in the July 2023 issue of the Thoracic Oncology by Hong et al.
The objective of this study was to assess the utility of programmed death-ligand 1 (PD-L1) copy number (CN) alteration as an additional biomarker to standard immunohistochemistry (IHC) in predicting response to immune checkpoint inhibitor (ICI) therapy in advanced NSCLC. Before ICI monotherapy, tumor PD-L1 CN alterations (gain, neutral, or loss) were determined using whole-exome sequencing data and compared to IHC results (tumor proportion score 50, 1–49, or 0). Survival without progression (PFS) and overall survival were correlated with both biomarkers.
In addition, the impact of CN modification was assessed in two independent cohorts using a panel of next-generation sequencing. The inclusion criteria were fulfilled by 291 patients with advanced-stage non-small cell lung cancer. The IHC classification distinguished the most responsive group (tumor proportion score ≥50), whereas the CN-based classification distinguished the least responsive group (CN loss) from the others (PFS, P = 0.020; overall survival, P = 0.004). CN loss was an independent risk factor for disease progression (adjusted hazard ratio = 1.32, 95% CI: 1.00–1.73, P = 0.049) and mortality (adjusted hazard ratio = 1.39, 95% CI: 1.05–1.85, P = 0.022).
Based on IHC and CN profiles, a risk classification system was devised that outperformed the conventional IHC system. In validation cohorts, CN loss, as determined by the next-generation sequencing panel, was independently associated with poorer PFS following ICI treatment, demonstrating its clinical utility. This is the first study to compare CN alterations with IHC results and survival outcomes following anti–PD-(L)1 therapy. Loss of tumor PD-L1 CN can be a supplementary biomarker for predicting a lack of response. Further validation of this biomarker requires prospective studies.
Source: sciencedirect.com/science/article/pii/S1556086423004823