Driving precision oncology in lung cancer: Patient stratification through comprehensive genomic profiling.

Abstract

8070 Background: Next Generation Sequencing (NGS)-guided targeted therapy is a standard practice in lung cancer, as recommended by professional guidelines. Various gene panels, exome, and genome sequencing strategies are employed to detect therapeutic targets. Selecting the right test is critical for achieving favorable patient outcomes. This study compares the efficacy and clinical utility of gene panels and exome sequencing in stratifying patients for different therapeutic options. Methods: We retrospectively analyzed genomic profiles of 1,224 advanced lung cancer patients (Stage III and Stage IV) sequenced using small gene panel (SP; 72 genes, NCCN biomarker driven TarGT First) and broad gene panel (BP; 1,212 genes, NCCN and pathways driven TarGT IndieGene. Tumor FFPE samples were screened for SNVs/InDels, CNVs, gene fusions, and immunotherapy biomarkers, including TMB, MSI, and PD-L1 expression. Results: Among the 1,224 patients, 791 were screened with small panels, 552 with broad panels, and 42 with exome sequencing. Sequencing with BP identified at least one driver/pathogenic mutation in 89.7% patients, which was higher than that detected in SP (73.6%). BP detected a higher proportion of patients with therapeutically targetable variants than SP (80.6% vs. 73.3%). Both SP and BP detected equivalent proportion of patients as eligible for level 1 (FDA-approved) therapy (SP 38.7% vs. BP 37.5%) and level 2 therapy (3.2% vs. 4%) and while a significantly higher number of patients eligible for level 3 (clinical trials) therapies were detected in BP (SP 31.5% vs. BP 39.1%). In a subset of 172 patients screened with both SP and BP. BP identified driver/pathogenic mutations in all patients (100% diagnostic yield) while SP identified mutations in 62.8% of the patients. BP also detected targetable variants in 84.9% of cases, compared to 62.8% detected in SP. Patients eligible for FDA-approved therapy (48.3% vs. 41.9%), off-label therapy (5.2% vs. 3.5%), and clinical trial therapies (38.4% vs. 17.4%) were more frequently detected with BP than in SP. Conclusions: BP outperform SP in detecting clinically significant drivers and therapeutic biomarkers, demonstrating their utility in precision oncology. This study highlights the advantages of comprehensive genomic profiling (CGP) over small panels for guiding prognosis and therapy decisions in advanced lung cancer during disease progression. Patients with targetable variants (No. of patients; %) Level 1 therapy(No. of patients; %) Level 2 therapy (No. of patients; %) Level 3 therapy (No. of patients; %) No therapy(No. of patients; %) Small panel sequencing (SP)(n=791 patients) 580; 73.3% 306; 38.7% 25; 3.2% 249; 31.5% 211; 26.7% Broad panel sequencing (BP)(n=552 patients) 445; 80.6% 207; 37.5% 22; 4% 216; 39.1% 107; 19.4%