P75.02 Non-Squamous NSCLC Patients Harbored STK11 or KEAP1 Mutation Showed Insensitivity to any Treatment Including Immunotherapy

Abstract

The objective of this study was mainly to analyze the prognostic effect for patients with non-squamous non-small cell lung cancer (NSCLC) harbored STK11 or KEAP1 mutation received chemotherapy and PD1/PD-L1 inhibitors. The data from OAK and POPLAR clinical trials was firstly applied to analyze the relationship between STK11 or KEAP1 mutation and PD-L1 expression and blood tumor mutation burden (bTMB) for patients with non-squamous NSCLC; Then, the overall survival (OS) difference was compared between the patients who received atezolizumab or docetaxel harbored STK11 or KEAP1 mutation and none. Importantly, the OS difference of patients between STK11 or KEAP1 mutation and none was further confirmed using public database from the cBioPortal platform. Most STK11 (7.33% vs.1.57%) or KEAP1 (10.76% vs. 8.46%) mutation was found in non-squamous NSCLC patients comparing with squamous NSCLC. Interestingly, only 0.96% STK11 mutation and 1.92% KEAP1 mutation occurred in EGFR mutated non-squamous NSCLC patients. Compared with wild-type, higher bTMB were found in patients harbored STK11 or KEAP1 mutation (both, P < 0.001), while PD-L1 expression was higher (25% VS. 14.54%) in KEAP1 mutated patients and lower (7.89% VS. 15.9%) in STK11 mutated patients. Importantly, we found that non-squamous NSCLC patients harbored STK11 or KEAP1 mutations had worse OS no matter treated with atezolizumab monotherapy or docetaxel (all, P < 0.001). Moreover, these mutated patients could not benefit from atezolizumab compared with docetaxel (all, P > 0.05). Similarly, in further analysis of cBioPortal data, we also found that STK11 or KEAP1 mutated non-squamous NSCLC patients who received PD1/PD-L1 inhibitors or other treatment had worse survival than wild-type (all, P < 0.05). Non-squamous NSCLC patients harbored STK11 or KEAP1 mutation were not sensitive to any treatment, suggesting they may be a special subtype.