Background: STK11 (also called LKB1) is among the 3 most mutated genes in lung adenocarcinoma, but its prognostic and predictive significance in advanced NSCLC patients is still not clear. Recent preclinical and translational evidence suggest its role in conditioning KRAS mutant lung adenocarcinomas aggressiveness and response to targeted treatment.
Materials and methods: This retrospective analysis, in a single center, included consecutive NSCLC patients who had undergone a platinum-containing regimen, for which standard or next generation (NGS) sequencing analyses of STK11 gene (exons 1-9) had been successfully performed. STK11 gene was considered mutated if effect on protein was predicted as deleterious. Clinical features along with EGFR (exons 18-21), KRAS (exons 2-4) and TP53 (exons 1-11) mutational status were correlated to STK11 status. Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis, adjusting for stage (advanced yes/no) and histology for progression-free survival (PFS), and smoking status, stage, EGFR/KRAS status and number of lines of chemotherapy for overall survival (OS).
Results: Among the 302 patients included between November 2007 and January 2015, 63% were male, 16% non-smoker and median age was 60 year; 75% had an adenocarcinoma, 88% a stage IIIB or IV and 80% no previous treatment for advanced disease; 25 (8%) patients had a STK11 mutation, 30 (10%) an EGFR mutation and 81 (27%) a KRAS mutation. Deletions/insertions, missense and false-sense mutations mainly involved exon 4-6 of STK11. No statistical differences were observed between STK11 status and sex, smoking status, age, stage at diagnosis or histology (adenocarcinoma versus others). Among the 25 patients with STK11 mutation, 13 patients (52%) had a KRAS mutation, compared with 67 (24%) among those without STK11 mutation (p = 0.008). No correlation between STK11 and EGFR or TP53 mutational status was observed. Median follow-up time was 34.8 months (95% confidence interval [CI95]: 30.7-42.3). In univariate analysis, OS was shorter for STK11 mutated patients compared to wild type ones (p = 0.085; HR: 1.53; CI95: 0.94-2.49) with a median OS of 10.4 (CI95: 6.1-15.7) and 17.3 (CI95: 14.0-21.1) months for mutated and wild-type STK11 patients respectively. In multivariate analysis, the HR was 1.21 (CI95: 0.74-1.99; p = 0.45). Similar non-significant results were observed for PFS.
Conclusion: We confirm the reported data of a positive correlation between STK11 and KRAS mutations. No correlation between STK11 status and PFS or OS in patients receiving platinum-based treatment was observed when taking into account other prognostic covariates.
Citation Format: Francesco Facchinetti, Maria Virginia Bluthgen, Gabrielle Tergemina Clain, Laura Faivre, Jean-Pierre Pignon, David Planchard, Jean-Charles Soria, Benjamin Besse, Ludovic Lacroix. STK11 mutations in non-small cell lung cancer (NSCLC): descriptive analysis and prognostic significance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2250.