均衡KRAS突变的III期非小细胞肺癌患者的预后差异：在同步放化疗基础上加用度伐利尤单抗可改善生存。
Equalizing prognostic disparities in KRAS-mutated stage III NSCLC patients: addition of durvalumab to combined chemoradiotherapy improves survival.
作者信息
Eklund Ella A, Orgard Mathilda, Wallin Delice, Sayin Sama I, Fagman Henrik, Isaksson Johan, Raghavan Sukanya, Akyürek Levent M, Nyman Jan, Wiel Clotilde, Hallqvist Andreas, Sayin Volkan I
机构信息
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
出版信息
Lung Cancer. 2025 Jun;204:108573. doi: 10.1016/j.lungcan.2025.108573. Epub 2025 May 2.
INTRODUCTION
Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group and identification of subgroups with differential treatment responses is crucial. Addition of durvalumab to concurrent chemoradiotherapy (cCRT) has previously been shown to improve survival outcomes. Meanwhile, subgroups harboring KRAS mutations have been shown to have worse prognosis. We investigated whether KRAS mutational status may affect survival outcomes after adjuvant durvalumab following cCRT in stage III NSCLC.
METHODS
In this multi-center retrospective study, we present a real-world dataset of all stage III NSCLC patients treated with curative-intent cCRT with molecular assessment, between 2016 and 2021 in the Västra Götaland Region of western Sweden. The study period includes the standard practice prior to the introduction of durvalumab, enabling evaluation of the potential impact of immune checkpoint blockade (ICB). Primary study outcomes were overall survival (OS) and progression free survival (PFS).
RESULTS
We identified 145 patients who received cCRT with curative intent, and 32 % harbored an activating mutation in the KRAS gene (KRAS; n = 46). Compared to patients with wild-type KRAS (KRAS; n = 99), KRAS had worse OS (p = 0.047) and PFS (p = 0.038). This finding persisted on multivariate analysis with OS (HR 1.703, 95 % CI 1.074-2.702, p = 0.024) and PFS (HR 1.628, 95 % CI 1.081-2.453, p = 0.020). Within the subgroup that received cCRT alone, KRAS patients (n = 35) exhibited worse OS (p = 0.036) and PFS (p = 0.037) compared with KRAS (n = 35). However, among those who received additional durvalumab after cCRT (KRAS; n = 99. KRAS; n = 11) there were no significant differences in OS (0.788) or PFS (0.855) between the groups.
CONCLUSIONS
KRAS mutations are a negative prognostic factor after cCRT in stage III NSCLC, and the addition of durvalumab ameliorates the negative impact of harboring this mutation.
引言
III期非小细胞肺癌（NSCLC）是一个异质性群体，识别具有不同治疗反应的亚组至关重要。先前已证明在同步放化疗（cCRT）中添加度伐利尤单抗可改善生存结果。同时，已证明携带KRAS突变的亚组预后较差。我们研究了KRAS突变状态是否会影响III期NSCLC患者在cCRT后辅助使用度伐利尤单抗的生存结果。
方法
在这项多中心回顾性研究中，我们呈现了2016年至2021年期间瑞典西部韦斯特罗斯-哥塔兰地区所有接受根治性cCRT并进行分子评估的III期NSCLC患者的真实世界数据集。研究期间包括引入度伐利尤单抗之前的标准治疗方法，从而能够评估免疫检查点阻断（ICB）的潜在影响。主要研究结局为总生存期（OS）和无进展生存期（PFS）。
结果
我们确定了145例接受根治性cCRT的患者，其中32%的患者KRAS基因存在激活突变（KRAS；n = 46）。与KRAS野生型患者（KRAS；n = 99）相比，KRAS突变患者的OS（p = 0.047）和PFS（p = 0.038）更差。这一发现经多因素分析后在OS（HR 1.703，95%CI 1.074 - 2.702，p = 0.024）和PFS（HR 1.628，95%CI 1.081 - 2.453，p = 0.020）方面仍然存在。在仅接受cCRT的亚组中，KRAS突变患者（n = 35）与KRAS野生型患者（n = 35）相比，OS（p = 0.036）和PFS（p = 0.037）更差。然而，在cCRT后接受额外度伐利尤单抗治疗的患者中（KRAS突变；n = 99，KRAS野生型；n = 11），两组之间的OS（0.788）或PFS（0.855）无显著差异。
结论
KRAS突变是III期NSCLC患者cCRT后的不良预后因素，添加度伐利尤单抗可改善携带该突变的负面影响。
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