Data from Combining Genomic Biomarkers to Guide Immunotherapy in Non–Small Cell Lung Cancer

• DOI: 10.1158/1078-0432.c.7158235
• Publication Date: 2024-04-01T07:24:00Z
• Authors: Joris van de Haar; Joanne M. Mankor; Karlijn Hummelink; Kim Monkhorst; Egbert F. Smit; Lodewyk F.A. Wessels; Edwin Cuppen; Joachim G.J.V. Aerts; Emile E. Voest

<div>AbstractPurpose:<p>The clinical value of <i>STK11</i>, <i>KEAP1</i>, and <i>EGFR</i> alterations for guiding immune checkpoint blockade (ICB) therapy in non–small cell lung cancer (NSCLC) remains controversial, as some patients with these proposed resistance biomarkers show durable ICB responses. More specific combinatorial biomarker approaches are urgently needed this disease.</p>Experimental Design:<p>To develop a strategy increased specificity unresponsiveness NSCLC, we performed comprehensive analysis 254 NSCLC treated ligand programmed death-ligand 1 (PD-L1) monotherapy, including discovery cohort 75 subjected to whole-genome sequencing (WGS), an independent validation 169 tumor-normal large panel sequencing. The <i>STK11</i>/<i>KEAP1</i>/<i>EGFR</i> was assessed the contexts low (<10 muts/Mb) or high (≥10 tumor mutational burden (TMB).</p>Results:<p>In TMB cases, were highly resistance, 0/15 (0.0%) 1/34 (2.9%) biomarker-positive showing treatment benefit cohorts, respectively. This contrasted where 11/13 (85%) 15/34 (44%) at least one alteration showed These findings supported by analyses progression-free survival overall survival.</p>Conclusions:<p>The unexpected responses carrying almost exclusively observed TMB. Considering context, offered limiting overtreatment NSCLC.</p></div>