美国布列根和妇女医院Ariadna Tibau团队研究了指南推荐的分子靶点和基因组靶向癌症治疗的临床价值。相关论文于2024年8月20日发表在《英国医学杂志》上。

为了评估国家癌症综合网络（NCCN）推荐用于临床实践的基因组靶向癌症药物的分子靶点的临床效益和可操作性，研究组根据NCCN指南在晚期环境中推荐的基因组靶向癌症药物进行了一项横断面研究。使用欧洲肿瘤医学会（ESMO）分子靶点临床可操作性量表（ESCAT）评估分子靶点可操作性。使用ESMO临床效益量表（ESMO-MCBS）评估基因组靶向肿瘤治疗的临床效益。与ESMO-MCBS（4-5级）显示出实质性临床益处的研究相关的ESCAT I类分子靶点被指定为高益处，与ESMO-MCFS 3级研究相关的分子靶点则被归类为有前景但未经证实的益处。

对411项建议进行了审查，这些建议涉及74种针对50种驱动因素改变的基因组靶向药物。大多数建议（346/411；84%）与不同阶段的临床试验有关，但16%（65/411）仅依赖病例报告或临床前研究。然而，临床试验主要包括I期或II期（271/346；78%）、单臂（262/346；76%）研究。大多数试验中评估的主要终点是总体缓解率（271/346；78%），而不是生存率。经济、社会和文化事务部一级目标能力涵盖了60%（246/411）的目标建议，35%（142/411）被归类为二级或三级，6%（23/411）的相关性尚未确定（四级至十级）。

当ESMO-MCBS应用于267项可评分试验时，只有12%（32/267）显示出实质性的临床益处（4-5级），45%（121/267）为3级。当两种框架结合使用时，12%（32/267）的试验支持确定高益处，33%（88/267）表示有前景但未经证实的效益。在NCCN作者推荐的118种干预措施中，62种（53%）适用于高益处或有希望但未经证实的益处的治疗。

研究结果表明，根据ESCAT和ESMO-MCBS框架，大约八分之一的基于基因组的癌症治疗被评为可能为患者提供高益处，而大约三分之一被确定为提供有希望但未经证实的实质性益处。确保NCCN的建议与预期的临床效益相一致，对于促进知情、循证、基因组指导的治疗决策至关重要。

附：英文原文

Title: Clinical value of guideline recommended molecular targets and genome targeted cancer therapies: cross sectional study

Author: Ariadna Tibau, Thomas J Hwang, Jerry Avorn, Aaron S Kesselheim

Issue&Volume: 2024/08/20

Abstract:

Objective To assess the clinical benefit and actionability of molecular targets for genome targeted cancer drugs recommended for clinical practice by the National Comprehensive Cancer Network (NCCN).

Design Cross sectional study.

Participants/setting Genome targeted cancer drugs recommended by NCCN guidelines in the advanced setting.

Main outcome measures Molecular target actionability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit of genome targeted oncology therapies was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets at ESCAT category level I associated with studies showing substantial clinical benefit by ESMO-MCBS (grades 4-5) were designated as high benefit, and those linked to studies achieving an ESMO-MCBS grade of 3 were categorized as being of promising but unproven benefit.

Results 411 recommendations related to 74 genome targeted drugs targeting 50 driver alterations were examined. Most recommendations (346/411; 84%) were associated with clinical trials of various phases, but 16% (65/411) relied on only case reports or pre-clinical studies. However, clinical trials mostly comprised phase I or phase II (271/346; 78%), single arm (262/346; 76%) studies. The primary endpoint assessed in most trials was overall response rate (271/346; 78%) rather than survival. ESCAT tier I targetability encompassed 60% (246/411) of target recommendations, 35% (142/411) were classified as tier II or III, and 6% (23/411) had their relevance yet to be determined (tiers IV to X). When ESMO-MCBS was applied to 267 scorable trials, only 12% (32/267) showed substantial clinical benefit (grades 4-5) and 45% (121/267) were grade 3. When both frameworks were combined, 12% (32/267) of trials supported a determination of high benefit and 33% (88/267) indicated promising but unproven benefit. Of the 118 interventions endorsed by NCCN authors as preferred, 62 (53%) applied to treatments with high or promising but unproven benefit.

Conclusion According to the ESCAT and ESMO-MCBS frameworks, about one eighth of genome based treatments for solid cancer were rated as likely to offer a high benefit to patients, whereas around a third were identified as offering a promising but unproven substantial benefit. Ensuring that NCCN recommendations are aligned with expected clinical benefits is crucial for promoting informed, evidence based, genomic guided treatment decisions.

DOI: 10.1136/bmj-2023-079126

Source: https://www.bmj.com/content/386/bmj-2023-079126