目前，在旨在评估难治性转移性结直肠癌 (mCRC) 患者新疗法的随机临床试验 (RCT) 中，对于具有临床意义的结果尚无共识定义。自2014年以来，多个学会发布了改善总生存期和无进展生存期的推荐目标，包括美国临床肿瘤学会（ASCO）2014年临床有意义的结果工作组、欧洲肿瘤内科学会-Magnitude 2015 年临床获益量表 (ESMO-MCBS) 和 2019 年加拿大结直肠癌 (CCC) 共识声明。然而，来自几项系统评价的证据表明，在导致肿瘤药物批准的相当大比例的随机对照试验中，推荐的阈值未满足 ASCO 和 ESMO-MCBS 要求。除了疗效和安全性之外，生活质量 (QoL) 对于转移性结直肠癌患者也很重要，特别是对于那些正在接受后期治疗或临终关怀的患者。因此，ESMO-MCBS 和 CCC 都建议将生活质量评估纳入 mCRC 临床试验的设计中。自2014年ASCO建议发布以来，难治性转移性结直肠癌患者的治疗方案开发取得了重大进展；其中包括批准曲氟尿苷/替匹拉西 (FTD/TPI) 作为单一药物并与贝伐单抗联合使用，以及批准呋喹替尼。在三线转移性结直肠癌的 III 期随机对照试验中，只有 FTD/TPI 加贝伐珠单抗的 SUNLIGHT 试验达到了临床有意义的改善的所有推荐阈值，同时与 FTD/TPI 相比，还证明了可控的安全性和多种生活质量指标的恶化速度较慢独自的。 SUNLIGHT 研究的结果表明，几个具有临床意义的终点的增量收益是可以实现的，从而提高了定义难治性 mCRC 新兴疗法的临床意义结果的标准。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Currently, there is no consensus definition for clinically meaningful outcomes in randomized clinical trials (RCTs) designed to evaluate new treatments for patients with refractory metastatic colorectal cancer (mCRC). Since 2014, recommended targets for improvements in overall survival and progression-free survival have been published by several societies, including those from the American Society of Clinical Oncology (ASCO) Clinically Meaningful Outcomes Working Group in 2014, the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) in 2015, and Colorectal Cancer Canada (CCC) consensus statements in 2019. However, evidence from several systematic reviews suggests that in a substantial proportion of RCTs that led to oncology drug approvals, the recommended thresholds of ASCO and ESMO-MCBS were not met. In addition to efficacy and safety, quality of life (QoL) is important to patients with mCRC, especially for those who are receiving later-line therapy or end-of-life care. As such, both ESMO-MCBS and CCC recommend the inclusion of QoL assessments in the design of mCRC clinical trials. Since the publication of the ASCO recommendations in 2014, there has been significant progress in the development of treatment options for patients with refractory mCRC; these include the approvals of trifluridine/tipiracil (FTD/TPI) as a single agent and in combination with bevacizumab, and the approval of fruquintinib. Among the phase III RCTs in third-line mCRC, only the SUNLIGHT trial of FTD/TPI plus bevacizumab met all recommended thresholds for clinically meaningful improvements, while also demonstrating a manageable safety profile and slower deterioration in multiple measures of QoL compared with FTD/TPI alone. The results from the SUNLIGHT study show that incremental gains in several clinically meaningful endpoints are achievable, thus raising the bar in defining clinically meaningful outcomes for emerging therapies in refractory mCRC.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.