Value of Delivery of Targeted Therapy for Veterans with Advanced Lung Cancer

描述（由申请人提供）： 背景/原理：肺癌是退伍军人癌症相关死亡的主要原因，VA每年诊断出约7，000例新病例。非小细胞肺癌（NSCLC）是最常见的类型，约占所有肺癌病例的85%。大多数新病例在最初表现时处于晚期癌症阶段。基于基因组的靶向治疗如厄洛替尼和克唑替尼正在成为肺癌患者的替代治疗选择。在我们了解NSCLC分子肿瘤生物学之前，常规治疗通常是标准化的、预先确定的、非个体化的全身铂类化疗方案。厄洛替尼在NSCLC患者中的临床疗效已通过随机临床试验得到证实。由于这些靶向药物的毒性较低，研究表明厄洛替尼治疗EGFR阳性NSCLC患者的临床结局和生活质量更好。然而，在VA医疗保健系统的常规实践中，对晚期NSCLC退伍军人的临床管理中靶向治疗的价值知之甚少。这项研究的目的是填补这些知识空白。目的：我们的具体目标是：1）检查基于基因组的靶向治疗在VA医疗保健系统内诊断为晚期NSCLC的退伍军人的临床管理中的利用; 2）检查在VA医疗保健系统内的总生存期方面，靶向治疗在退伍军人肺癌管理中的临床有效性; 3）评估在VA医疗保健系统内，相对于常规护理，在肺癌退伍军人管理中提供靶向治疗的成本和成本效益;（4）调查VHA肺癌患者对基因组靶向治疗的认知、态度、促进因素和障碍。方法：拟议项目是一项使用VA临床和管理数据的观察性队列研究。将从VA中央癌症登记研究中确定诊断为NSCLC的合格研究患者，并随访至死亡或研究结束时删失。成果措施包括：总生存月数、与癌症治疗相关的不良事件、治疗成本和每增加一个生命月的增量成本。暴露变量是自诊断为肺癌的患者以来厄洛替尼使用的时变指标。当比较厄洛替尼与常规治疗的临床有效性时，患者的人口统计学、肿瘤特征以及合并症和机构特征将被用作混杂因素。将进行描述性分析和多变量回归模型以及定性研究，以解决所述特定目标。预期研究结果将使我们更好地了解退伍军人肺癌靶向治疗的临床有效性和成本效益，以及肿瘤学家对肺癌靶向治疗的看法。本研究中获得的知识将用于告知政策决策者、临床医生、研究人员和肺癌患者关于在VA医疗保健系统中提供基于基因组的靶向治疗用于肺癌治疗的价值。

DESCRIPTION (provided by applicant): Background/Rationale: Lung cancer is the leading cause of cancer-related deaths among Veterans and about 7,000 newly cases are diagnosed yearly in VA. Non-small cell lung cancer (NSCLC) is the most common type and accounts for approximately 85% of all lung cancer cases. Majority of new cases are in advanced cancer stages at the initial presentation. The genomic-based for targeted therapy such as erlotinib and crizotinib is emerging as an alternative treatment option for patients diagnosed with lung cancer. Prior to our understanding of NSCLC molecular tumor biology, conventional treatment has generally been standardized, predetermined, non-individualized protocols of systemic platinum-based chemotherapy. Clinical efficacy of erlotinib has demonstrated through randomized clinical trials in patients with NSCLC. Because of lower toxicity profiles in these targeted agents, studies demonstrated that patients with EGFR-positive NSCLC treated with erlotinib had better clinical outcomes and quality of life. However, little is known about values of the delivery of targeted therapy in clinical management for Veterans with advanced NSCLC in routine practice in the VA healthcare system. The goal of the proposed study is to fill these gaps in knowledge. Objectives: Our specific aims are: 1)To examine utilization of the genomic-based targeted therapy in clinical management of Veterans diagnosed with advanced NSCLC within the VA healthcare system; 2) to examine clinical effectiveness of the delivery of targeted therapy in management of Veterans with lung cancer in terms of overall survival within the VA healthcare system; 3) to assess cost and cost-effectiveness of the delivery of targeted therapy in management of Veterans with lung cancer relative to the conventional care within the VA healthcare system; and 4) to examine knowledge, attitude, facilitators and barriers of delivering genomic-based targeted therapy for patients with lung cancer at the VHA. Methods: The proposed project is an observational cohort study using VA clinical and administrative data. Eligible study patients diagnosed with NSCLC will be identified from the VA Central Cancer Registry and followed until death or censored at the end of study. The outcome measures include: overall survival month, adverse events associated with the cancer treatment, treatment cost, and incremental cost per additional life- month gained. The exposure variable is a time-varying measure of the use of erlotinib since patients diagnosed with lung cancer. Patients' demographics, tumor characteristics and comorbidity and facility characteristics will be used as confounding factors when compare clinical effectiveness of erlotinib to the conventional care. Descriptive analyses and multivariate regression models, and qualitative study will be performed to address the stated specific aims. Expected findings of the proposed study will provide us a better understanding about clinical effectiveness and cost-effectiveness of targeted therapy for Veterans with lung cancer, and oncologists' perceptions on use of targeted therapy for lung cancer. Knowledge gained in this study will be used to inform policy decision-maker, clinicians, researchers and lung cancer patients about values of delivering genomic- based targeted therapy for lung cancer treatment in the VA healthcare system.