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早期表皮生长因子受体突变的非小细胞肺癌治疗的最新进展与新见解

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer.

作者信息

Sotelo Miguel J, Luis García José, Torres-Mattos Cesar, Milián Héctor, Carracedo Carlos, González-Ruiz María Ángeles, Mielgo-Rubio Xabier, Trujillo-Reyes Juan Carlos, Couñago Felipe

机构信息

Department of Medical Oncology, Hospital María Auxiliadora; Department of Medical Oncology, Centro Oncológico Aliada; Oncological Research Unit, Clínica San Gabriel, Lima 15801, Peru.

Department of Thoracic Surgery, Hospital Universitario La Princesa; Department of Thoracic Surgery, MD Anderson Cancer Center; Department of Thoracic Surgery, Hospital HM, Madrid 28006, Spain.

出版信息

World J Clin Oncol. 2021 Oct 24;12(10):912-925. doi: 10.5306/wjco.v12.i10.912.

Abstract

Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

摘要

早期非小细胞肺癌(NSCLC)患者是根治性手术的候选对象;然而,尽管肺癌治疗取得了多项进展,但复发率仍然很高。辅助化疗已被证明可显著延长总生存期(OS),但这种益处并不显著,迫切需要有效的新疗法来治愈更多患者。酪氨酸激酶抑制剂(TKIs)对晚期表皮生长因子受体突变(EGFR)的非小细胞肺癌患者具有高效性,这促使人们在疾病早期对这些药物进行评估。多项临床试验评估了EGFR TKIs作为辅助治疗在切除的EGFR突变NSCLC患者中的安全性和有效性,结果表明它们可显著延长无病生存期(DFS),但这种益处并未转化为总生存期的延长。最近,ADAURA试验的中期分析表明,令人惊讶的是,奥希替尼改善了DFS。这导致该研究提前终止,关于其对总生存期的潜在影响以及作为该患者亚组标准辅助治疗的纳入,仍有许多问题未得到解答。这些靶向药物也正在局部晚期疾病中进行评估,结果令人鼓舞,不过需要更大样本量的前瞻性研究来证实这些结果。在本文中,我们回顾了关于EGFR TKIs在早期EGFR突变NSCLC治疗中作用的最相关研究。

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