48P Real-world clinical utility of next-generation sequencing ctDNA for patients with advanced lung squamous cell carcinoma

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) can identify a wide spectrum of genomic alterations (GAs), guiding treatment decisions in patients (pts) with non-small cell lung cancer (NSCLC), especially with adenocarcinoma histology. However, the clinical utility of NGS in pts with lung squamous cell carcinoma (L-SCC) remains controversial. We report the clinical utility of ctDNA-based NGS in a cohort of advanced L-SCC, according to the ESMO ESCAT scale of actionability. This was a multicenter retrospective study including treatment-naïve pts with advanced L-SCC with plasma ctDNA NGS performed (InVisionFirst-Lung®) between Feb 2018 and Dec 2022. Clinical actionability was classified according to the ESCAT scale; Tier I (ready for clinical implementation), Tier II (alteration-drug match with antitumor activity), Tier III (supported in other tumor types/similar alterations), and Tier IV (preclinical evidence). We defined clinically informative results as ESCAT tier I/II/III. A total of 131 pts with advanced L-SCC underwent NGS-ctDNA at 13 institutions in the United States, Canada, France, and Spain. Median age was 73 (range, 45-97), and 2/3 were male. Smoking history data was not available. At diagnosis, ≥1 ctDNA GA was detected in 68% (87/128; 3 failed); TP53 mutation (mut) was the most frequent GA (48%). NGS-ctDNA provided clinically informative results for 33 pts (26%); 5 (4%) were ESCAT tier I (2 BRAFV600E mut, 1 ALK fusion, 1 EGFR exon (ex) 19 deletion, 1 MET ex14 skipping mut), 3 (2%) ESCAT tier IIB (1 KRASG12D mut, 1 KRASG12V mut, 1 KRASG12R mut) and 25 (20%) ESCAT tier III (9 PIK3CA mut, 6 FGFR1 amplifications, 5 EGFR amplifications, 2 KRASG12A mut, 1 IDH1 mut, 1 HRAS mut, 1 NRAS mut). Additionally, NGS-ctDNA detected GAs classified as ESCAT IV (7 CDKN2A mut, 4 PTEN mut, 2 KRAS G13C mut, 1 KRAS G61K mut) in 14 pts (11%). NGS-ctDNA provided clinically informative results for 26% of pts with advanced lung SCC, including 6% for whom targeted therapies are available in routine practice or clinical trials (4% ESMO ESCAT tier I and 2% ESMO ESCAT tier IIB). These results suggest that molecular profiling, including plasma NGS testing, should be considered in this population.