Chuang Jody C, Salahudeen Ameen A, Wakelee Heather A
a Division of Hematology and Oncology , Stanford Hospital & Clinics , Stanford , CA , USA.
b Department of Medicine, Division of Oncology , Stanford University School of Medicine , Stanford , CA , USA.
Expert Opin Pharmacother. 2016;17(7):989-93. doi: 10.1517/14656566.2016.1162786. Epub 2016 Apr 4.
Major advances have been made since the discovery of driver mutations and their targeted therapies, especially in the treatment of patients with epidermal growth factor receptor (EGFR) mutations. Despite their initial efficacy in the majority of the patients with such driver mutations, all targeted therapies are limited by the eventual development of resistance mechanisms.
EGFR T790M mutation is a common resistance mechanism after treatment with first or second generation EGFR tyrosine kinase inhibitors (TKI). Rociletinib is one of the third generation EGFR TKIs with activity against T790M and activating EGFR mutations while sparing the wild-type EGFR. In this review, we discuss the current understanding and available data on rociletinib, including the side effects associated with the medication. We will also review the BEAMing plasma test to detect T790M mutation without the need for repeat biopsy. Lastly, we review the potential resistance mechanisms after progression on rociletinib, and future directions.
It is important to note that there are other 3(rd) generation EGFR TKIs with activity against T790M already approved by the US FDA (osimertinib) and many others in development. Future research will focus on figuring out which patients can benefit the most from a particular medication with minimal side effects, and further resistance mechanisms after rociletinib.
自从发现驱动基因突变及其靶向治疗方法以来，尤其是在治疗表皮生长因子受体（EGFR）突变患者方面取得了重大进展。尽管这些靶向治疗方法在大多数此类驱动基因突变患者中最初具有疗效，但所有靶向治疗都受到耐药机制最终发展的限制。
EGFR T790M突变是第一代或第二代EGFR酪氨酸激酶抑制剂（TKI）治疗后的常见耐药机制。罗西替尼是第三代EGFR TKI之一，对T790M和激活型EGFR突变具有活性，同时保留野生型EGFR。在本综述中，我们讨论了关于罗西替尼的当前认识和现有数据，包括与该药物相关的副作用。我们还将回顾用于检测T790M突变而无需重复活检的BEAMing血浆检测。最后，我们回顾了罗西替尼治疗进展后的潜在耐药机制以及未来方向。
需要注意的是，美国食品药品监督管理局（FDA）已经批准了其他对T790M具有活性的第三代EGFR TKI（奥希替尼），并且还有许多其他药物正在研发中。未来的研究将集中于确定哪些患者能够从特定药物中获益最大且副作用最小，以及罗西替尼治疗后的进一步耐药机制。
