Yoneda Kazue, Imanishi Naoko, Ichiki Yoshinobu, Tanaka Fumihiro
Second Department of Surgery (Chest Surgery), School of Medicine, University of Occupational and Environmental Health, Japan.
J UOEH. 2019;41(2):153-163. doi: 10.7888/juoeh.41.153.
The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene and development of tyrosine kinase inhibitors (TKIs) of EGFR have achieved a paradigm shift in treatment strategy of non-small cell lung cancer (NSCLC). For advanced NSCLC harboring activating EGFR mutations, an EGFR-TKI is preferably prescribed as it provides a superior survival benefit over platinum-based chemotherapy. To further improve the therapeutic outcomes, more potent EGFR-TKIs through irreversible inhibition of tyrosine kinase have been developed. In a recent clinical trial, an irreversible EGFR-TKI (osimertinib) showed a superior survival benefit with lower toxicity profile. In addition, combination treatments such as an EGFR-TKI plus platinum-based chemotherapy may achieve a long-term survival. For earlier-stage resectable NSCLC with EGFR-mutations, several clinical trials to assess the efficacy of EGFR-TKIs in pre-operative induction setting and in postoperative adjuvant setting are now ongoing. Here we review and discuss the current status and future perspectives of treatment for EGFR-mutated NSCLC.
表皮生长因子受体(EGFR)基因激活突变的发现以及EGFR酪氨酸激酶抑制剂(TKIs)的研发,实现了非小细胞肺癌(NSCLC)治疗策略的范式转变。对于携带EGFR激活突变的晚期NSCLC患者,优先开具EGFR-TKI,因为它比铂类化疗具有更好的生存获益。为了进一步提高治疗效果,已经开发出通过不可逆抑制酪氨酸激酶作用更强的EGFR-TKIs。在最近的一项临床试验中,一种不可逆的EGFR-TKI(奥希替尼)显示出更好的生存获益且毒性更低。此外,联合治疗如EGFR-TKI加铂类化疗可能实现长期生存。对于早期可切除的EGFR突变NSCLC,目前正在进行多项评估EGFR-TKIs在术前诱导和术后辅助治疗中疗效的临床试验。在此,我们综述并讨论EGFR突变NSCLC治疗的现状和未来展望。