Khan Adam, Khan Hassan, Hughes Griffin K, Ladd Chase, McIntire Ryan, Gardner Brooke, Peña Andriana M, Schoutko Abigail, Tuia Jordan, Minley Kirstien, Haslam Alyson, Prasad Vinay, Vassar Matt
Office of Medical Student Research, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, USA.
Department of Internal Medicine, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, USA.
Cancer Med. 2024 May;13(9):e7130. doi: 10.1002/cam4.7130.
This study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients.
The burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence-based protections for trial participants, and improve medical decision-making.
On May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate.
Ramucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression-free survival for patients were 1.5 and 1.2 months, respectively. FDA-approved indications have reported more positive outcomes in comparison to off-label indications.
We found that FDA-approved indications for ramucirumab had better efficacy outcomes than non-approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.
本研究旨在评估已发表的雷莫西尤单抗临床试验，以评估患者的风险/获益情况及长期负担。
肿瘤药物研发给患者带来的负担，加之临床试验失败率不断上升，凸显了药物研发改革的必要性。识别并解决过度负担模式可指导政策制定，确保为试验参与者提供基于证据的保护，并改善医疗决策。
2023年5月25日，在PubMed/MEDLINE、Embase、Cochrane CENTRAL和ClinicalTrials.gov上进行文献检索，查找使用雷莫西尤单抗作为单一疗法或与其他干预措施联合用于癌症治疗的临床试验。作者以盲法、重复的方式筛选标题和摘要以确定潜在纳入的研究。经过数据筛选后，以盲法、重复的方式提取数据。试验在达到其主要终点和安全性标准时被分类为阳性，阴性或不确定。
雷莫西尤单抗最初被批准用于胃癌，但此后已在其FDA批准适应症之外的20种癌症中进行了测试。在我们对雷莫西尤单抗试验的分析中，共有10936名参与者，报告了10303起不良事件。患者的总生存期和无进展生存期分别增加了1.5个月和1.2个月。与非标签适应症相比，FDA批准的适应症报告了更多积极结果。
我们发现，雷莫西尤单抗的FDA批准适应症比未批准适应症具有更好的疗效结果。然而，在所有评估的试验中都观察到了数量令人担忧的不良事件。与对照组相比，雷莫西尤单抗随机对照试验的参与者在总生存期方面获益甚微。鉴于其毒性负担和生存获益不佳，临床医生应仔细权衡雷莫西尤单抗治疗相关的风险。
