1127P Efficacy of current immunotherapies in patients (pt) with metastatic non-small cell lung cancer (NSCLC) harboring KRAS mutations

Approximately 20% of lung adenocarcinomas harbor KRAS mutations (mut), an oncogene that has the ability to alter the tumor immune microenvironment. The most common mut found in ∼40% of cases is KRAS G12C, which has been related with tobacco exposure. Despite the immune-related nature of KRAS driven tumors, they are genomically heterogenous and the efficacy of immunotherapy (IT) according to KRAS mut type has not been well elucidated. The objective of this study is to describe a cohort with KRAS-mutant NSCLC treated with IT and evaluate the clinical outcomes. A retrospective cohort of KRAS-mutated NSCLC pt treated at the Catalan Institute of Oncology Badalona between June/2013 and March/2022 were included. KRAS was determined by cobas® KRAS mut test, a real-time PCR test designed for the identification of mut in codons 12, 13 and 61; NGS panels (Oncomine Solid) in the most recent cases. PD-L1 status in tumor cells was determined by immunohistochemistry assay (VENTANA PD-L1 SP263) and was categorized: negative <1%, low 1-49% and high ≥50%. Chi-square test for categorical variables and Kaplan Meier method for survival analysis were performed. Of the 103 pt included: 73% were male, median age at diagnosis: 62. 97% were current/former smokers, 69% had stage IV at diagnosis. KRAS mutation type: 47% harbored KRAS G12C and 52% KRAS nonG12C. PD-L1 status was available in 76% of cases: 39% high, 19% low, 19% negative. High PD-L1 was predominantly found in KRAS G12C vs nonG12C (64% vs 36%, p=0.01). All pt were treated with IT (97% with antiPD(L)1 based regimens): 54% in 1st line, 36% in 2nd and 10% in ≥3rd. 15% received chemo-IT. After median follow up of 26.5m, differences in median progression free survival (mPFS) to IT were observed whether they received IT in 1st, 2nd or ≥3rd line: 23.1m vs 3.2m vs 5.9m, respectively (p=0.036). mPFS to IT according to KRAS G12C vs nonG12C was 10.1 vs 16.7 m, p=0.78; mOS in G12C vs nonG12C was 32.6 vs 26.3m, p=0.37. KRAS mut represent a heterogenous group of NSCLC. Although KRAS G12C mut tumors exhibited higher PDL1 expression, no differences were observed in mPFS nor mOS compared to KRAS nonG12C in our cohort. Starting 1st line IT improved mPFS, regardless of KRAS mut type, with no impact on OS.