Reyes Amanda, Pharaon Rebecca, Mohanty Atish, Kim Jae, Massarelli Erminia
Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.
Transl Lung Cancer Res. 2025 May 30;14(5):1870-1876. doi: 10.21037/tlcr-2024-1197. Epub 2025 May 21.
Lung cancer has the highest mortality rate world-wide, but treatments for non-small cell lung cancer (NSCLC) including immune check point inhibitors and targeted tyrosine kinase inhibitors have greatly improved survival. Many of the targeted tyrosine kinase inhibitors have already been approved in the first line in metastatic disease. The use of combination chemotherapy and immunotherapy treatment in the perioperative setting has been highly successful, but patients with driver alterations were largely left out including patients with mesenchymal epithelial transition exon 14 ( Ex14) mutations. There are on-going randomized controlled clinical trials evaluating targeted kinase inhibitors in the perioperative setting. We also provide an in-depth overview of the MET pathway as well as the current state of -targeted peri-operative treatment in lung cancer and highlight the relevant trials.
We discuss the rationale and clinical course of the use of neoadjuvant and adjuvant tepotinib in a case study of an elderly patient with a Ex14 mutation in surgically resectable stage IIB N0 NSCLC, who was not an optimal candidate for traditional chemotherapy for several reasons.
From the single case report, we found that tepotinib was both safe and effective when used in the neoadjuvant setting with no evidence of recurrence after greater than one year of post-operative follow up. Adjuvant treatment was not as well tolerated and therefore stopped. We conclude with a discussion on the advantages and potential downfalls of -targeted tyrosine kinase inhibitors in the perioperative setting as well as some potential new areas of investigation.
肺癌是全球死亡率最高的癌症,但包括免疫检查点抑制剂和靶向酪氨酸激酶抑制剂在内的非小细胞肺癌(NSCLC)治疗方法已大大提高了生存率。许多靶向酪氨酸激酶抑制剂已被批准用于转移性疾病的一线治疗。围手术期联合化疗和免疫治疗已取得了巨大成功,但驱动基因改变的患者,包括间充质上皮转化外显子14(Ex14)突变的患者,在很大程度上被排除在外。目前正在进行随机对照临床试验,以评估围手术期靶向激酶抑制剂的疗效。我们还深入概述了MET通路以及肺癌围手术期靶向治疗的现状,并重点介绍了相关试验。
我们在一个病例研究中讨论了使用新辅助和辅助替泊替尼的基本原理和临床过程。该病例为一名老年患者,患有可手术切除的IIB期N0 NSCLC且存在Ex14突变,由于多种原因,该患者并非传统化疗的最佳候选者。
从该单病例报告中,我们发现替泊替尼在新辅助治疗中既安全又有效,术后随访一年多无复发迹象。辅助治疗的耐受性较差,因此停止了治疗。我们最后讨论了围手术期靶向酪氨酸激酶抑制剂的优点和潜在缺点,以及一些潜在的新研究领域。