Jiang Liyang, Meng Xiangjiao, Zhao Xianguang, Xing Ligang, Yu Jinming
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Transl Lung Cancer Res. 2020 Oct;9(5):2137-2144. doi: 10.21037/tlcr-20-722.
The standard treatment of unresectable locally advanced non-small cell lung cancer (LA NSCLC) is concurrent chemoradiotherapy. With the addition of immunotherapy, patients with LA NSCLC received a significantly prolonged outcome, while patients with harboring epidermal growth factor receptor (EGFR) mutation benefited less. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of stage IV with harboring EGFR mutation and anaplastic lymphoma kinase rearrangement, but there are few recommendations indicating whether TKI treatment is effective in unresectable NSCLC. Preclinical studies have shown that TKIs could have a radiosensitizing effect, which provided a rationale to consider the application TKI with radiotherapy. In this review, we summarize the clinical studies that have used TKIs in LA-NSCLC as well as ongoing trials, and discuss recent progress in research related to the efficacy of TKI for unresectable LA NSCLC patients. Recent results of small studies evaluating TKI therapy for LA NSCLC patients in combination with radiation or chemoradiation demonstrated promising efficacy, improved outcomes with a tolerable toxicity profile. However, there is a lack of strong evidence for TKI treatment in unresectable LA NSCLC, because of unpowered statistics, lack of molecular selection, or lack of large randomized arms. We prospect the combination of TKI and radiation or chemoradiation therapy might eventually replace the current standard treatment for patients with LA NSCLC harboring oncogene-driven mutation.
不可切除的局部晚期非小细胞肺癌（LA NSCLC）的标准治疗方法是同步放化疗。随着免疫疗法的加入，LA NSCLC患者的生存期显著延长，而携带表皮生长因子受体（EGFR）突变的患者获益较少。酪氨酸激酶抑制剂（TKIs）彻底改变了IV期携带EGFR突变和间变性淋巴瘤激酶重排患者的治疗方式，但对于TKI治疗在不可切除的NSCLC中是否有效，几乎没有相关推荐。临床前研究表明，TKIs可能具有放射增敏作用，这为考虑将TKI与放疗联合应用提供了理论依据。在本综述中，我们总结了在LA-NSCLC中使用TKIs的临床研究以及正在进行的试验，并讨论了与TKI对不可切除的LA NSCLC患者疗效相关的研究进展。近期评估TKI疗法联合放疗或同步放化疗用于LA NSCLC患者的小型研究结果显示出有前景的疗效，在可耐受的毒性特征下改善了预后。然而，由于统计效能不足、缺乏分子筛选或缺乏大型随机分组，在不可切除的LA NSCLC中缺乏TKI治疗的有力证据。我们预期，TKI与放疗或同步放化疗的联合应用最终可能会取代目前针对携带致癌基因驱动突变的LA NSCLC患者的标准治疗方法。
