医学
结直肠癌
帕尼单抗
肿瘤科
背景(考古学)
养生
中止
临床试验
表皮生长因子受体抑制剂
内科学
封锁
癌症
克拉斯
表皮生长因子受体
受体
古生物学
生物
作者
Davide Ciardiello,Gianluca Mauri,Andrea Sartore-Bianchi,Salvatore Siena,Maria Giulia Zampino,Nicola Fazio,Andrés Cervantes
标识
DOI:10.1016/j.ctrv.2024.102683
摘要
Abstract
Despite recent molecular and immunological advancements, prognosis of metastatic colorectal cancer (mCRC) patients remains poor. In this context, several retrospective and phase II studies suggested that after failure of an upfront anti-EGFR based regimen, a subset of patients can still benefit from further anti-EGFR blockade. Several translational studies involving circulating tumor DNA (ctDNA) analysis demonstrated that cancer clones harboring mutations driving anti-EGFR resistance, which can arise under anti-EGFR agents selective pressure, often decay after anti-EGFR discontinuation potentially restoring sensitivity to this therapeutic strategy. Accordingly, several retrospective analyses and a recent prospective trial demonstrated that ctDNA RAS and BRAF wild-type mCRC patients are those benefitting the most from anti-EGFR rechallenge. Indeed, in molecularly selected patients, anti-EGFR rechallenge strategy achieved up to 30 % response rate, with a progression free survival longer than 4 months and an overall survival longer than 1 year, which favorably compared with other standard therapeutic options available for heavily pretreated patients. Anti-EGFR is also well tolerated with no unexpected toxicities compared to the upfront setting. However, several open questions remain to be addressed towards a broader applicability of anti-EGFR strategy in the everyday clinical practice such as the identification of the best rechallenge regimen, the right placement in mCRC therapeutic algorithm, the best ctDNA screening panel. In our systematic review, we revised available data from clinical trials assessing anti-EGFR rechallenge activity in chemo-refractory mCRC patients, discussing as well potential future scenarios and development to implement this therapeutic approach. Particularly, we discussed the role of ctDNA as a safe, timely and comprehensive tool to refine patient's selection and the therapeutic index of anti-EGFR rechallenge.
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