A Multi-Institute Survivorship Study of Patients Living with Advanced Cancer Who Have Had Durable Response to Immune Checkpoint Inhibitors

对免疫检查点抑制剂有持久反应的晚期癌症患者的多机构生存研究

• 批准号: 10714336
• 负责人: Charles Stewart Kamen
• 金额: $ 81.59万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-14 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714336
• 关键词: Address; Adopted; Advanced Malignant Neoplasm; Age; Behavioral; Biological Markers; Body Composition; California; Cancer Center; Cancer Survivorship; Caring; Clinical; Communities; Companions; Comprehensive Cancer Center; Data; Diagnosis; Dimensions; Disease; Disease remission; Disseminated Malignant Neoplasm; Enrollment; Ethnic Origin; Evidence based intervention; FDA approved; Health behavior; Immune checkpoint inhibitor; Immune response; Immunotherapeutic agent; Immunotherapy; In complete remission; Inferior; Infusion procedures; Intervention; Learning; Life Style; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of lung; Metastatic Melanoma; Modeling; Mutation; Patient Care; Patient Outcomes Assessments; Patients; Phase; Population; Predictive Factor; Preparation; Prognosis; Progression-Free Survivals; Prospective cohort; Psychosocial Factor; Quality of life; Race; Renal carcinoma; Sister; Survivors; Symptoms; Telomere Length Maintenance; Therapeutic; Universities; Unresectable; advanced disease; behavioral health; cancer diagnosis; cancer immunotherapy; cancer therapy; cancer type; checkpoint therapy; clinical practice; clinical predictors; cohort; demographics; design; follow-up; improved; ipilimumab; melanoma; partial response; patient population; predictive marker; programmed cell death ligand 1; psychosocial; psychosocial wellbeing; racial disparity; response; sex; side effect; survival prediction; survivorship; tumor

ABSTRACT Immune checkpoint inhibitors (ICIs) have markedly transformed the therapeutic landscape for many types of advanced malignancies over the past decade. A sizable proportion of patients with advanced cancer derive durable benefits from ICIs and achieve longer periods of progression-free survival or remission than previously possible. Yet we still know little about the determinants of durable response to ICI treatment and the symptom trajectory and survivorship needs of this growing patient population. We thus propose a multi-institute study with two sister cohorts of patients living with advanced cancers. First, a retrospective EHR data-only cohort will include 8,860 patients with advanced disease, inclusive of all cancer types, who have been treated with ICI- based immunotherapy in 2014-2022. This large cohort will allow us to identify and study durable responders to ICIs, defined as patients who achieve partial or complete response to ICI treatment and live at least one year after ICI treatment initiation. Second, a prospective cohort will enroll and actively follow an estimated 1,200 patients with durable response to ICI treatment for advanced lung cancer, kidney cancer, and melanoma, the three most common cancers treated with ICIs. Clinical and patient-reported outcome data will be collected at baseline and every 6 months during follow up. This prospective cohort will allow us to study long-term survival and physical and psychosocial symptom trajectories in patients with durable response to ICIs, and to identify clinical and modifiable behavioral factors predictive of long-term survival and common side effects of ICI treatment. The predictors identified in these analyses will be independently validated in the DiRECT Cohort, a large ongoing study of racial disparities in ICI treatment led by the study team. Our Specific Aims are: 1. In the retrospective EHR data-only cohort, 1a) Determine the proportion of patients who had durable response to ICI treatment (partial/complete response and alive ≥1 year since initial ICI treatment) and chart their survival trajectory; 1b) Identify clinical predictors for durable response to ICI treatment; 1c). In the independent DiRECT Cohort, validate the clinical predictors for durable response to ICI treatment. 2. In the prospective cohort, 2a) Identify long-term survival and longitudinal trajectories of patients' physical and psychosocial symptoms after ICI treatment; 2b) Investigate the relationships of long-term survival and common side effects from ICI treatment with multidimensional predictors; 2c). In the independent DiRECT Cohort, validate the predictors for survival and common side effects in patients with durable response. Findings from our study will provide much-needed data that can inform new evidence-based intervention strategies as the next step to optimize survivorship care and extend and improve quality of life for the growing population of survivors living after a diagnosis of advanced cancer due to ICI treatment.

摘要 免疫检查点抑制剂（ICI）已经显著改变了许多类型的免疫缺陷的治疗前景。 在过去十年中，晚期恶性肿瘤。相当大比例的晚期癌症患者 ICIs的持久获益，并实现比以前更长的无进展生存期或缓解期 可能然而，我们对ICI治疗的持久反应的决定因素和症状仍然知之甚少。 这一不断增长的患者群体的轨迹和生存需求。因此，我们建议进行多机构研究 与两组晚期癌症患者的姐妹队列进行比较。首先，一个回顾性的EHR数据队列将 包括8，860名晚期疾病患者，包括所有癌症类型，他们接受了ICI治疗， 2014-2022年的免疫治疗。这个大的队列将使我们能够识别和研究持久的反应者， ICI，定义为对ICI治疗达到部分或完全缓解且存活至少1年的患者 ICI治疗开始后。第二，一个前瞻性队列将招募并积极随访估计1，200名 对ICI治疗晚期肺癌、肾癌和黑色素瘤有持久反应的患者， 三种最常见的用ICIs治疗的癌症临床和患者报告的结局数据将在 基线和随访期间每6个月。这个前瞻性队列将使我们能够研究长期生存率 以及对ICI有持久反应的患者的身体和心理社会症状轨迹，并确定 预测ICI长期生存和常见副作用的临床和可改变的行为因素 治疗这些分析中确定的预测因子将在DireCT队列中独立验证， 由研究小组领导的关于ICI治疗中种族差异的大型正在进行的研究。我们的具体目标是： 1.在仅回顾性EHR数据队列中，1a）确定具有持久性 对ICI治疗的应答（部分/完全应答，自初始ICI治疗后存活≥1年）和图表 它们的生存轨迹; 1b）确定对ICI治疗的持久反应的临床预测因子; 1c）.在 独立的DireCT队列，验证ICI治疗持久应答的临床预测因子。 2.在前瞻性队列中，2a）确定患者的长期生存和身体状况的纵向轨迹 ICI治疗后的心理社会症状; 2b）研究长期生存和 ICI治疗的常见副作用与多维预测因子; 2c）。在独立的Direct 队列研究，验证持久缓解患者的生存和常见副作用的预测因子。 我们的研究结果将提供急需的数据，为新的循证干预提供信息。 战略作为下一步，以优化生存护理，延长和提高生活质量的增长 由于ICI治疗而诊断为晚期癌症后生活的幸存者人群。