Use of genomic sequencing for the determination of genomic alterations and new therapeutic opportunities in Spanish lung cancer (LC) patients (pts)

LC is the leading cause of cancer death worldwide. The accurate determination of genomic alterations can provide valuable information to find the best therapeutic approach for each pts. Thus, Foundation Medicine services were used to determine the genomic profile of Spanish LC pts with no previously identified mutations by immunohistochemistry in clinical practice. Genomic profiling of LC pts who are likely to be refractory to previous treatments was carried out with FoundationOne® CDx (F1CDx) assay on DNA from tumour tissue or by FoundationOne®Liquid (F1Liquid) assay on circulating tumour DNA (ctDNA) from blood. Based on the results obtained, new therapeutic approaches and clinical trials were recommended. A total of 508 samples were analysed; 209 (41%) with F1CDx and 299 (59%) with F1Liquid. Overall, the most prevalent histologic diagnosis was adenocarcinoma (61%). The most common genomic alterations found in tumour tissue were tumour high mutational burden (TMB, 27%), EGFR (12%), ERBB2 (6%) and NF1 (6%), while in ctDNA were high TMB (13%), EGFR (18%), ERBB2 (3%) and MET (3%) (Table). Actionable alterations with at least one sensitizing therapy recommendation were detected in 57% of the solid samples and 42% of the ctDNA samples (Table). Actionable alterations with at least one clinical trial recommendation were detected in 89% and 68% of the tumour and ctDNA samples, respectively. Immunotherapies were recommended in 36.4% of pts, and targeted therapies in 62.6%.Table: 1101PGenomic alterations and therapy recommendations in solid and liquid samplesSolid samples (n=209)Liquid samples (n=299)Genomic alterationsTherapy recommendationsGenomic alterationsTherapy recommendationsTMB27%47%13%30%EGFR12%25%18%57%ERBB26%4%3%3%NF16%2%2%2%MET4%1%3%1%BRAF4%2%2%1%ALK4%10%1%5%RET3%2%2%1%NTRK12%1%-1%MAP2K11%1%--ROS11%3%--CD2741%1%--NRAS1%-1%-HRAS1%---NF21%---STK111%--- Open table in a new tab To date, this is the largest study characterizing the genomic profile of Spanish LC pts in this setting. Our results show that pts without previously identified mutations in clinical practice and scarce therapeutic alternatives could benefit from a more sensitive diagnostic tool and tailored therapeutic strategy recommendations.