Clinically meaningful outcomes in refractory metastatic colorectal cancer: a decade of defining and raising the bar

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-10-11 DOI:10.1016/j.esmoop.2024.103931

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引用次数: 0

Abstract

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.

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难治性转移性结直肠癌中具有临床意义的结果：十年来对标准的定义和提高

目前，对于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）中有临床意义的结果，还没有达成共识的定义。自 2014 年以来，多个学会发布了总生存期和无进展生存期改善的推荐目标，包括 2014 年美国临床肿瘤学会 (ASCO) 临床有意义结果工作组、2015 年欧洲肿瘤内科学会临床获益量表 (ESMO-MCBS) 和 2019 年加拿大结直肠癌学会 (CCC) 的共识声明。然而，多篇系统综述的证据表明，在相当一部分导致肿瘤药物获批的 RCT 中，并没有达到 ASCO 和 ESMO-MCBS 推荐的阈值。除了疗效和安全性外，生活质量（QoL）对 mCRC 患者也很重要，尤其是那些接受晚期治疗或临终关怀的患者。因此，ESMO-MCBS 和 CCC 都建议在设计 mCRC 临床试验时纳入 QoL 评估。自2014年ASCO建议发布以来，难治性mCRC患者治疗方案的开发取得了重大进展；其中包括批准三氟尿苷/替吡拉西（FTD/TPI）作为单药和与贝伐珠单抗联用，以及批准fruquintinib。在针对三线mCRC的III期临床试验中，只有FTD/TPI联合贝伐珠单抗的SUNLIGHT试验达到了临床意义改善的所有推荐阈值，同时还显示出了可控的安全性，并且与单用FTD/TPI相比，多项QoL指标的恶化速度更慢。SUNLIGHT研究的结果表明，几项有临床意义的终点指标的增益是可以实现的，从而提高了难治性mCRC新兴疗法有临床意义结果的定义标准。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.