Use of Patient-Reported Outcomes in Understanding Symptomatic Adverse Events in Early-Phase Trials of Combination Treatments that Include Immune Checkpoint Inhibitors and Targeted Therapy

使用患者报告的结果来了解包括免疫检查点抑制剂和靶向治疗在内的联合治疗早期试验中的症状不良事件

基本信息

批准号：
10533725
负责人：
Goldy C George
金额：
$ 14.68万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-05 至 2025-11-30
项目状态：
未结题

项目摘要

PROJECT SUMMARY Breakthroughs in cancer immunotherapy have excited patients and clinicians and have brought optimism back into the oncology community. However, these therapies are often effective for only a percentage of patients, and some patients may even be at risk for serious and sometimes fatal toxicities related to the therapy. Unlike the toxicities induced by standard therapies, immune-related adverse events (irAEs) are just becoming appreci- ated, and side effect profiles for new immunotherapies are often poorly understood. Further contributing to this issue is the increasing use of therapies that combine immune checkpoint inhibitors approved by the US Food and Drug Administration (eg, nivolumab, pembrolizumab) with other checkpoint inhibitors or targeted thera- pies. The unique toxicities of such combination therapies remain largely unknown and need to be tracked, so that their immune-related safety profiles can be characterized and adequately managed. Researchers at The Uni- versity of Texas MD Anderson Cancer Center propose to use patient-reported outcomes (PROs) to capture symptomatic irAEs of combination therapies that include checkpoint inhibitors, taking advantage of the large number of early-phase trials of these therapies already in place in the institution's Department of Investigational Therapeutics, coupled with the expertise in longitudinal symptom assessment in the Department of Symptom Research. The Specific Aims of the study are: (1) to identify, track, and evaluate emerging symptomatic toxic- ities and symptom burden during early-phase clinical trials of treatments that include immune checkpoint in- hibitors in combination with other checkpoint inhibitors or targeted therapies; and (2) to investigate relation- ships between longitudinal patient-reported symptoms and clinical outcomes (eg, development of moderate-to- severe irAEs, time to treatment discontinuation, time to deterioration) in early-phase trials of combination treat- ments that include checkpoint inhibitors, and to investigate whether moderate to severe irAEs are predicted by increases in relevant symptoms prior to the event. The study's clinical impact will be early detection of irAEs associated with combination therapies that include checkpoint inhibitors, to facilitate proactive intervention. Worsening symptoms may presage the emer- gence of their clinical manifestations and allow for appropriate supportive care or for other treatment decisions to be made. PROs are an essential component of cancer drug development, without which clinicians and regu- lators have an incomplete picture of how patients are affected by a new agent. PROs will provide invaluable pa- tient perspectives on the symptomatic effects of combination treatments that include immune checkpoint in- hibitors to multiple stakeholders in early drug development (eg, patients, sponsors, regulators, and payers). This project addresses Recommendation F in the Cancer Moon Shot Blue Ribbon Panel 2016 report, which calls for accelerated research to monitor and manage patient-reported symptoms, not only for improving quality of life, but also for ensuring patient adherence to treatments that will improve therapeutic response. 1

项目概要癌症免疫疗法的突破让患者和临床医生兴奋不已，带来了乐观情绪回到肿瘤学界。然而，这些疗法通常仅对一小部分患者有效，有些患者甚至可能面临与治疗相关的严重甚至有时致命的毒性风险。不像标准疗法引起的毒性、免疫相关不良事件（irAE）刚刚开始受到重视人们对新免疫疗法的过时和副作用通常知之甚少。进一步为此做出贡献问题是越来越多地使用美国食品和药物管理局批准的结合免疫检查点抑制剂的疗法与其他检查点抑制剂或靶向治疗联合用药（例如纳武单抗、派姆单抗）馅饼。这种联合疗法的独特毒性在很大程度上仍然未知，需要追踪，因此他们的免疫相关安全性特征可以被表征并得到充分管理。大学的研究人员德克萨斯大学 MD 安德森癌症中心提议使用患者报告的结果 (PRO) 来捕获包括检查点抑制剂在内的联合疗法的症状性 irAE，利用大量的优势该机构的研究部门已经开展了这些疗法的早期试验数量治疗，加上症状科纵向症状评估的专业知识研究。该研究的具体目标是：（1）识别、跟踪和评估新出现的症状性毒性包括免疫检查点在内的治疗的早期临床试验期间的特征和症状负担抑制剂与其他检查点抑制剂或靶向治疗组合； (2) 调查关系- 纵向患者报告的症状和临床结果之间的关系（例如，中度至中度的发展）联合治疗早期试验中的严重 irAE、停止治疗时间、恶化时间）包括检查点抑制剂的药物，并研究是否可以通过以下方法预测中度至重度 irAE：事件发生前相关症状增加。该研究的临床影响将是早期检测与联合疗法相关的 irAE，包括检查点抑制剂，以促进主动干预。症状恶化可能预示着即将出现的情况其临床表现的发生情况，并考虑到适当的支持性护理或其他治疗决策待制作。 PRO 是癌症药物开发的重要组成部分，没有它，临床医生和监管机构医生对于新药物如何影响患者的情况并不完整。 PRO 将提供宝贵的资源对包括免疫检查点在内的联合治疗的症状影响的观点早期药物开发中多个利益相关者（例如患者、申办者、监管者和付款人）的抑制剂。该项目解决了 2016 年 Cancer Moon Shot Blue Ribbon Panel 报告中的建议 F，呼吁加速研究以监测和管理患者报告的症状，而不仅仅是为了改善生活质量，同时也确保患者坚持治疗以改善治疗反应。 1