Serine/threonine kinase 11 (STK11) mutations and immunotherapy resistance in patients with non-small cell lung cancer.

Abstract

e15055 Background: There is immune evasion and resistance to checkpoint inhibitors (CPI). Programmed death-ligand 1 (PD-L1) and Tumor mutational burden (TMB) might help us predict response, but we have not yet validated biomarkers that can predict resistance. Mutations (mut) in STK11 can induce epigenetic changes that confer proliferative advantages to cancer cells and preliminary reports have suggested that they can confer resistance to CPI. We investigated the role of STK11 and KRAS mut as markers of poor response to CPI in patients (pts) with non-small cell lung cancer (NSCLC). Methods: Clinical outcomes of 127 pts with stage IIIB-IV NSCLC who were tested for KRAS and STK11 mut and received CPI were evaluated for progression free survival (PFS) and overall survival (OS). For statistical analysis log-rank tests were used to compare OS and PFS, chi-squared tests were used to compare 1-year survivals and proportions among different variables, and Kaplan-Meier survival curves were used to report OS and PFS. Results: Of the 127 pts: 31 had STK11 mut, 14 had STK11+KRAS mut (SKM group), and 10 pts were in the SKMP group (STK11+KRAS mut+PD-L1 (-)). Median age was 65y (27-88y). Males were 54% of the total and 30 pts (24%) were Hispanic (H). STK11 mut patients had an inferior PFS and OS as shown in table. Pts in SKM and SKMP groups had worse outcomes; however, not all the P values were significant. The difference in OS and 1-year OS were very impressive and significant when compared between the SKMP group (4m and 30%) and the wild type group (15m and 73%). There were no significant differences in clinical outcomes for H vs. non-H White pts. Conclusions: The presence of STK11 mut were associated with shorter OS/PFS in NSCLC pts treated with CPIs, proving its utility as a negative predictive marker. This can be enhanced combining STK11 and KRAS mut and possibly adding PD-L1 (-). These findings are consistent with recent studies that have reported STK11 mut as a genomic driver of primary resistance. Due to the small sample size further studies will be needed to validate these findings. [Table: see text]