肺癌是全球死亡率最高的恶性肿瘤,其中非小细胞肺癌(Non-small Cell Lung Cancer,NSCLC)占85％.表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)基因是NSCLC中最常见的驱动基因之一.人表皮生长因子受体酪氨酸激酶抑制剂(Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors,EGFR-TKIs)给EGFR基因敏感突变患者的治疗带了突破性进展.但是,EGFR-TKIs的耐药性问题日益突出,临床急需用于EGFR-TKI治疗中或治疗后出现进展并伴有EGFR T790M阳性突变的NSCLC患者的治疗药物.洛奇替尼(Rociletinib)拟定位于解决这一尚未被满足的临床需求,但是由于本品的有效性并不优于已上市的同类药物,存在较高的安全性风险(高血糖、QT间期延长和猝死),且给药剂量未被美国食品药品监督管理局(Food and Drug Administration,FDA)认可,最终未能上市.本文从审评角度分析和总结本案例的经验教训,供业界争鸣.%Lung cancer is the highest mortality rate of malignancies in the world.Among them,non-small cell lung cancer (NSCLC) accounts for 85％.Epidermal growth factor receptor (EGFR) gene is one of the most common driving genes in NSCLC.The EGFR tyrosine kinase inhibitors (EGFR-TKIs) bring a breakthrough in the treatment for patients with EGFR gene-sensitive mutations.However,the drug resistance problem of EGFR-TKIs has been increasingly highlighted.So a drug for the patients accompanied by EGFR T790M positive mutation and along with progression in or after treatment with EGFR-TKI NSCLC is clinically urgent needed.Rociletinib is designed to address this unmet clinical need.While considering the non-superior effectiveness to the similar drugs in the market and the high risk of safety (hyperglycemia,QT prolongation and sudden death) of Rociletinib,the dosage was not accepted by the Food and Drug Administration (FDA).And Rociletinib did not make it to the market eventually.This paper discussed lessons learned from this case under review perspective for reference and inspiration.
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