Liu Jason, Amini Arya, Govindarajan Ameish, Abuali Tariq, Mambetsariev Isa, Massarelli Erminia, Villaflor Victoria, Villalona-Calero Miguel, West Howard, Williams Terence, Salgia Ravi
Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA.
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA.
JCO Precis Oncol. 2023 Sep;7:e2200445. doi: 10.1200/PO.22.00445.
With increased adoption of next-generation sequencing, tailored therapy on the basis of molecular status is being delivered for patients with early-stage resectable non-small-cell lung cancer (NSCLC). The purpose of this narrative review was to focus on recent developments of targeted therapies in the adjuvant and neoadjuvant/adjuvant setting for early-stage disease.
A systematic search of the MEDLINE/PubMed database was performed, focusing on studies published within the past 10 years. Our search queried "early-stage NSCLC (AND) tyrosine kinase inhibitor (TKI; OR) epidermal growth factor receptor (EGFR; OR) anaplastic lymphoma kinase ()" and was limited only to prospective and ongoing studies.
Most studies examining the benefit of targeted therapies in early-stage resectable NSCLC have been for EGFR-TKIs in the adjuvant setting. Currently, only one study, the ADAURA trial of adjuvant osimertinib, has demonstrated an overall survival benefit with the use of an EGFR-TKI in the adjuvant setting. Future work to build on the success of the ADAURA trial is focused on determining the optimal duration of targeted therapies and using biomarkers, such as circulating tumor DNA, to risk-stratify patients and guide maintenance targeted therapy duration.
The results of several ongoing studies are eagerly awaited regarding the use of targeted therapies in the neoadjuvant/adjuvant setting and for more uncommon or rare mutations such as , proto-oncogene 1, rearranged during transfection, mesenchymal-epithelial transition factor, and proto-oncogene V600E. The treatment landscape for early-stage NSCLC harboring actionable mutations is likely to shift dramatically in the upcoming decade.
随着下一代测序技术的广泛应用，基于分子状态的个体化治疗正在为早期可切除非小细胞肺癌（NSCLC）患者提供。本叙述性综述的目的是关注早期疾病辅助和新辅助/辅助治疗中靶向治疗的最新进展。
对MEDLINE/PubMed数据库进行系统检索，重点关注过去10年内发表的研究。我们的检索词为“早期NSCLC（与）酪氨酸激酶抑制剂（TKI；或）表皮生长因子受体（EGFR；或）间变性淋巴瘤激酶（）”，且仅限于前瞻性和正在进行的研究。
大多数评估靶向治疗对早期可切除NSCLC益处的研究是关于辅助治疗中的EGFR-TKI。目前，只有一项研究，即辅助奥希替尼的ADAURA试验，证明了在辅助治疗中使用EGFR-TKI可带来总生存获益。在ADAURA试验成功的基础上开展的未来工作重点在于确定靶向治疗的最佳持续时间，并使用循环肿瘤DNA等生物标志物对患者进行风险分层，以指导维持靶向治疗的持续时间。
关于在新辅助/辅助治疗中使用靶向治疗以及针对更罕见或少见突变（如转染重排的原癌基因1、间充质上皮转化因子和原癌基因V600E）的多项正在进行的研究结果备受期待。在未来十年，携带可操作突变的早期NSCLC的治疗格局可能会发生巨大变化。
