Equalizing prognostic disparities in KRAS-mutated stage III NSCLC patients: addition of durvalumab to combined chemoradiotherapy improves survival

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2025-05-02 DOI:10.1016/j.lungcan.2025.108573

Ella A. Eklund , Mathilda Orgard , Delice Wallin , Sama I. Sayin , Henrik Fagman , Johan Isaksson , Sukanya Raghavan , Levent M. Akyürek , Jan Nyman , Clotilde Wiel , Andreas Hallqvist , Volkan I. Sayin

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引用次数: 0

Abstract

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^MUT; n = 46). Compared to patients with wild-type KRAS (KRAS^WT; n = 99), KRAS^MUT 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^MUT patients (n = 35) exhibited worse OS (p = 0.036) and PFS (p = 0.037) compared with KRAS^WT (n = 35). However, among those who received additional durvalumab after cCRT (KRAS^WT; n = 99. KRAS^MUT; 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.

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平衡kras突变的III期NSCLC患者的预后差异：在联合放化疗中加入durvalumab可提高生存率

III期非小细胞肺癌（NSCLC）是一个异质性群体，鉴别具有不同治疗反应的亚群是至关重要的。durvalumab加入同步放化疗（cCRT）之前已被证明可以改善生存结果。同时，携带KRAS突变的亚群预后较差。我们研究了KRAS突变状态是否会影响III期NSCLC cCRT后辅助杜伐单抗的生存结果。在这项多中心回顾性研究中，我们提供了2016年至2021年间在瑞典西部Västra Götaland地区接受具有治愈意图的cCRT治疗的所有III期NSCLC患者的真实数据集，并进行了分子评估。研究期间包括引入durvalumab之前的标准实践，能够评估免疫检查点阻断（ICB）的潜在影响。主要研究结果是总生存期（OS）和无进展生存期（PFS）。结果145名接受cCRT治疗的患者中，32%的患者携带KRAS基因激活突变(KRASMUT；n = 46)。与野生型KRAS患者(KRASWT；n = 99)， KRASMUT的OS （p = 0.047）和PFS （p = 0.038）较差。这一发现在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）的多变量分析中仍然存在。在单独接受cCRT的亚组中，KRASMUT患者（n = 35）的OS （p = 0.036）和PFS （p = 0.037）比KRASWT （n = 35）更差。然而，在cCRT后接受额外杜伐单抗的患者中(KRASWT；n = 99。KRASMUT;n = 11)，两组间OS（0.788）和PFS（0.855）差异无统计学意义。结论skras突变是III期NSCLC cCRT后的一个负面预后因素，而durvalumab的加入改善了携带该突变的负面影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.