P2.09-28 Prognostic Impact of LKB1 Expression in Advanced Non-Small-Cell Lung Cancer

Abstract

LKB1 is a tumor suppressor gene that regulates cell energy homeostasis, cell polarization, and apoptosis. Within lung cancer, LKB1 ranks as the third most common mutation found in lung adenocarcinoma, both alleles are somatically inactivated in 30%. LKB1 mutations are linked to smoking history, moreover, it have been associated with more aggressive clinical phenotype in KRAS-mutant NSCLC patients, according to preclinical models. Additionally, LKB1 has been associated with primary resistance to PD-1 axis inhibitors in lung adenocarcinoma. However, its expression and clinical implication has not been extensively studied. The aim of the study was to evaluate LKB1 expression in patients with advanced NSCLC. In retrospective way patients with advanced NSCLC with and without EGFR mutations from México and Colombia were analyzed. Patients received therapy according EGFR status (TKI anti-EGFR or chemotherapy). Inclusion criteria were a histopathological confirmed diagnosis, adequate tissue to determine the expression of LKB1 by immunohistochemistry through the clone HPA017254 (Sigma®). The primary outcome was overall survival (OS). A total of 87 patients were included in the analysis, 25.3% of them had LKB1 positive expression. Median score intensity was 20%. There was a significant association of LKB1 positive expression with wood-smoke exposure (76.9 vs 23.1%, p≤0.001), EGFR mutation (54.5 vs 45.5%, p≤0.001) compared to LKB1 negative. Global Median OS was 29.7 months. Median OS for LKB1 positive was 33.3 months (CI 95%, 8.9 - 57.6) and 29.5 months (CI 95%, 26.1 - 32-8) for LKB1 negative (p=0.42). After stratifying patients by percentage of LKB1 expression, cut-off of 20% showed a tendency to increase OS in patients with ≥20% expression (figure 1); 49.9 months (IC 95%, 10.6 - 85.2 months) vs 29.5 months (IC 95%, 26.3 - 32.7 months), (p=0.068). Furthermore, a similar trend in OS was observed in patients with ≥50% expression, median OS was not reached compared with 29.5 months (IC 95%, 26.2 - 32.7 months) in patients with <50% expression (p=0.091). We found a trend to higher OS in patients with LKB1 expression >20%. This data should be confirmed in prospective study in order to determine the role of LKB1 as biomarker in NSCLC patients.