Abstract 918: Real-world clinical characteristics and treatment (tx) outcomes by co-mutation status in patients (pts) with KRAS G12C -mutated non-small cell lung cancer (NSCLC)

Background: KRAS mutations occur in ~30% of NSCLC and KRAS G12C is the most common subtype (~40%). Co-mutations can impact NSCLC prognosis and tx response. Methods: This retrospective study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine clinico-genomic database (FH-FMI CGDB; January 1, 2011 to March 31, 2022). De-identified data originated from ~280 US cancer clinics (~800 sites of care). This study is based on tissue-based assay (FoundationOne CDx). Pts were aged ≥18 years; had KRAS G12C-mutated, advanced/metastatic NSCLC, and had received ≥1 line of tx, with 1L tx initiated after October 1, 2016. Pts were categorized by presence (m) or absence (wt) of single co-mutations in STK11, KEAP1, or TP53; pts with EGFR, ALK, ROS1, BRAF, MET, or NTRK alterations were excluded. Key endpoints included overall survival (OS) and real-world progression-free survival (rwPFS). Statistical methods included a univariate Cox hazard model. Results: Among 847 pts with KRAS G12C-mutated NSCLC, co-mutations of STK11 were seen in 24%, KEAP1 in 14%, and TP53 in 51%. Based on non-missing records (82%), low tumor mutational burden (