对具有罕见可靶向驱动基因突变的早期非小细胞肺癌切除术后结果的分析

Analysis of outcomes in resected early-stage NSCLC with rare targetable driver mutations.

作者信息

Ghazali Nadia, Feng Jamie, Hueniken Katrina, Khan Khaleeq, Balaratnam Karmugi, Waddell Thomas K, Yasufuku Kazuhiro, Pierre Andrew, Donahoe Laura, Wakeam Elliot, Cypel Marcelo, Yeung Jonathan, Keshavjee Shaf, de Perrot Marc, Leighl Natasha B, Liu Geoffrey, Bradbury Penelope A, Sacher Adrian, Eng Lawson, Stockley Tracy, Tsao Ming Sound, Shepherd Frances A

机构信息

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre (PMCC), University Health Network (UHN), Toronto, ON, Canada.

University of Toronto, Toronto, ON, Canada.

出版信息

Ther Adv Med Oncol. 2024 Dec 23;16:17588359241308466. doi: 10.1177/17588359241308466. eCollection 2024.

DOI:10.1177/17588359241308466

PMID:39734710

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11672496/

Abstract

BACKGROUND

Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.

OBJECTIVES

This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.

METHODS

This retrospective single-center study identified stage I-III NSCLC patients with rare targetable mutations who underwent curative surgery. Tissue-based molecular profiling identified mutations in G12C, Exon20, Erb-B2 receptor tyrosine kinase 2 (), , , B-Raf proto-oncogene () V600E, mesenchymal-epithelial transition factor () exon14 skipping, and rearranged during transfection (). Baseline patient and tumor characteristics, mutation subtype, and co-mutation were correlated with RFS and OS using Cox regression. The G12C cohort was used as the reference for survival comparisons.

RESULTS

Among 225 patients, mutations included the following: G12C ( = 101, 45%), exon 14 skipping ( = 26, 12%), Exon 20 ( = 25, 11%), ( = 25, 11%), fusion ( = 16, 7%), fusion ( = 14, 6%), V600E mutation ( = 13, 6%), and fusion ( = 5, 2%). Five-year survival probabilities were 76% for stage I, 60% for stage II, and 58% for stage III. RFS was shorter across most mutation subgroups compared to G12C, with mutations showing significantly poorer RFS (HR 2.70, = 0.019). By contrast, all mutation subgroups were associated with better OS than G12C. The incidence of brain metastasis was highest in (22% at 5 years). TP53 co-mutation was associated with significantly worse OS (HR 2.35, = 0.008).

CONCLUSION

While RFS was poorer for most mutations compared to G12C, OS generally was better, suggesting a potential role for postoperative targeted therapies. These findings warrant further investigation through prospective studies and clinical trials to optimize adjuvant treatment strategies for patients with early-stage NSCLC harboring rare driver mutations.

摘要

背景

鉴于非小细胞肺癌（NSCLC）辅助治疗在表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）靶向治疗方面取得的进展，考虑对其他早期致癌基因成瘾性NSCLC进行术后靶向治疗很重要。探索具有这些罕见突变的早期NSCLC的基线结局至关重要。

目的

本研究旨在评估切除的具有罕见可靶向驱动突变的早期NSCLC患者的无复发生存期（RFS）和总生存期（OS）。

方法

这项回顾性单中心研究纳入了接受根治性手术的I-III期具有罕见可靶向突变的NSCLC患者。基于组织的分子谱分析确定了G12C、外显子20、Erb-B2受体酪氨酸激酶2（）、、、B-Raf原癌基因（）V600E、间充质-上皮转化因子（）外显子14跳跃以及转染期间重排（）中的突变。使用Cox回归分析基线患者和肿瘤特征、突变亚型以及共突变与RFS和OS的相关性。将G12C队列用作生存比较的参考。

结果

在225例患者中，突变情况如下：G12C（n = 101，45%）、外显子14跳跃（n = 26，12%）、外显子20（n = 25，11%）、（n = 25，11%）、融合（n = 16，7%）、融合（n = 14，6%）、V600E突变（n = 13，6%）以及融合（n = 5，2%）。I期患者的5年生存概率为76%，II期为60%，III期为58%。与G12C相比，大多数突变亚组的RFS较短，其中突变的RFS显著更差（HR 2.70，P = 0.019）。相比之下，所有突变亚组的OS均优于G12C。脑转移发生率在中最高（5年时为22%）。TP53共突变与OS显著更差相关（HR 2.35，P = 0.008）。