背景:STK11/LKB1突变与PD-1轴抑制剂的原发性耐药和晚期KRAS突变型肺腺癌的不良预后相关。本研究旨在评估STK11/LKB1改变在局部非鳞状非小细胞肺癌(非sNSCLC)中的预后意义。
方法:IIa期完全切除患者的手术样本,IIb,对随机辅助II期试验(NCT00775385IFCT-1801TASTE试验)中的IIIa(N2除外)非sqNSCLC进行了检查.患者接受标准化疗(培美曲塞顺铂)或基于EGFR突变(厄洛替尼)和ERCC1表达的个性化治疗。使用靶向NGS分析肿瘤分子谱,并与总生存期(OS)和无病生存期(DFS)相关。调整相关临床变量。此外,治疗组之间的相互作用和OS上的分子改变,PD-L1表达,术后血浆样本中的肿瘤循环DNA进行了评估。
结果:在134名患者(主要是男性吸烟者患有腺癌)中,KRAS突变与较短的DFS(HR:1.95,95%CI:1.1-3.4,p=0.02)和OS(HR:2.32,95%CI:1.2-4.6,p=0.014)相关。分离的STK11/LKB1突变(n=18)没有显著影响DFS或OS。然而,在KRAS突变的样品中(n=53),同时发生STK11/LKB1突变的患者(n=10)的DFS显著缩短(HR:3.85,CI:1.5~10.2,p=0.006),OS有缩短的趋势(HR:1.80,CI:0.6~5.3,p=0.28).PD-L1表达之间没有发现关联,其他基因突变,无进展生存期(PFS),或操作系统。
结论:该分析加强了KRAS突变作为局部非sNSCLC复发和生存不良的预测因素。此外,同时存在的STK11/LKB1突变加重了KRAS突变亚组的预后.这些发现强调了这些分子标志物的临床相关性及其对非sqNSCLC治疗策略的潜在影响。
STK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This
study aimed to assess the prognostic significance of STK11/LKB1 alterations in localized non-squamous non-small cell lung carcinoma (non-sq NSCLC).
Surgical samples from patients undergoing complete resection for stage IIa, IIb, or IIIa (N2 excluded) non-sq NSCLC in the randomized adjuvant phase II
trial (NCT00775385 IFCT-1801 TASTE
trial) were examined. Patients received either standard chemotherapy (Pemetrexed Cisplatin) or personalized treatment based on EGFR mutation (Erlotinib) and ERCC1 expression. Tumor molecular profiles were analyzed using targeted NGS and correlated with overall survival (OS) and disease-free survival (DFS), adjusting for relevant clinical variables. Additionally, interactions between treatment groups and molecular alterations on OS, PD-L1 expression, and tumor-circulating DNA in post-operative plasma samples were evaluated.
Among 134 patients (predominantly male smokers with adenocarcinoma), KRAS mutations were associated with shorter DFS (HR: 1.95, 95 % CI: 1.1-3.4, p = 0.02) and OS (HR: 2.32, 95 % CI: 1.2-4.6, p = 0.014). Isolated STK11/LKB1 mutations (n = 18) did not significantly impact DFS or OS. However, within KRAS-mutated samples (n = 53), patients with concurrent STK11/LKB1 mutations (n = 10) exhibited significantly shorter DFS (HR: 3.85, CI: 1.5-10.2, p = 0.006) and a trend towards shorter OS (HR: 1.80, CI: 0.6-5.3, p = 0.28). No associations were found between PD-L1 expression, other gene mutations, progression-free survival (PFS), or OS.
This analysis reinforces KRAS mutations as predictive factors for relapse and poor survival in localized non-sq NSCLC. Furthermore, the presence of concomitant STK11/LKB1 mutations exacerbated the prognosis within the KRAS-mutated subset. These findings emphasize the clinical relevance of these molecular markers and their potential impact on treatment strategies in non-sq NSCLC.