STK11 Mutations and Immunotherapeutic Efficacy in NSCLC

By: Vanessa A. Carter, BS
Posted: Wednesday, May 29, 2024

Jie He, PhD, of the First Affiliated Hospital of Chengdu Medical College, Sichuan, China, and colleagues performed a comprehensive study to evaluate the effect of serine/threonine kinase (STK11) mutations on the prognosis of patients with non–small cell lung cancer (NSCLC), including the efficacy of different therapeutic options. Published in BMC Cancer, the results of this study suggest that future trials should focus on tackling the resistance of STK11 mutations to PD-L1 immunotherapies in this subgroup of patients with STK11-mutant NSLCL.

“Patients with STK11-mutant NSCLC had low PD-L1 expression and objective response rates to immune checkpoint inhibitors, and their progression-free survival and overall survival were worse than [those of] patients with STK11 wild-type after comprehensive treatment,” concluded the investigators.

This analysis included 14 retrospective studies focusing on 4,317 patients with NSCLC; 605 patients had STK11 mutations. Data on hazard ratios (HR), positive rates of PD-L1 expression, survival, and objective response rate of immune checkpoint inhibitors were extracted and analyzed from each article. The association between clinical characteristics and STK11 mutation status was obtained through public databases and NSCLC data sets.

The study authors found that STK11 mutations were associated with poor progression-free survival (HR = 1.49) and overall survival (HR = 1.44). This was supported by the bioinformatics analysis, which further demonstrated that progression-free survival (P < .001) and overall survival (P = .002) were significantly worse in patients with STK11 mutations than in those without such mutations. The positive rate of PD-L1 expression in patients with STK11 mutations was 41.1%, and the objective response rate to immune checkpoint inhibitors was 10.1%. Of note, the authors suggested that drugs such as vinorelbine, fluorouracil, and the MDM2 inhibitor nutlin 3a may produce better sensitivity in patients with STK11 mutations.

Disclosure: The study authors reported no conflicts of interest.

BMC Cancer

---