End Points and Trial Design in Geriatric Oncology Research: A Joint European Organisation for Research and Treatment of Cancer-Alliance for Clinical Trials in Oncology-International Society of Geriatric Oncology Position Article

Harvey Jay Cohen, Duke University, Durham
Journal of Clinical Oncology (Impact Factor: 18.43). 09/2013; 31(29). DOI: 10.1200/JCO.2013.49.6125
Source: PubMed


Selecting the most appropriate end points for clinical trials is important to assess the value of new treatment strategies. Well-established end points for clinical research exist in oncology but may not be as relevant to the older cancer population because of competing risks of death and potentially increased impact of therapy on global functioning and quality of life. This article discusses specific clinical end points and their advantages and disadvantages for older individuals.Randomized or single-arm phase II trials can provide insight into the range of efficacy and toxicity in older populations but ideally need to be confirmed in phase III trials, which are unfortunately often hindered by the severe heterogeneity of the older cancer population, difficulties with selection bias depending on inclusion criteria, physician perception, and barriers in willingness to participate. All clinical trials in oncology should be without an upper age limit to allow entry of eligible older adults. In settings where so-called standard therapy is not feasible, specific trials for older patients with cancer might be required, integrating meaningful measures of outcome. Not all questions can be answered in randomized clinical trials, and large observational cohort studies or registries within the community setting should be established (preferably in parallel to randomized trials) so that treatment patterns across different settings can be compared with impact on outcome. Obligatory integration of a comparable form of geriatric assessment is recommended in future studies, and regulatory organizations such as the European Medicines Agency and US Food and Drug Administration should require adequate collection of data on efficacy and toxicity of new drugs in fit and frail elderly subpopulations.

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    • "Although older patients account for a majority of patients, they are often undertreated with standard chemotherapy regimens, largely due to a perception of poorer performance status, comorbidities, and anticipated intolerance to toxicity from platinum-based chemotherapy (Hardy et al, 2009;Davidoff et al, 2010;Langer, 2011). In addition, few studies have assessed treatment effects on quality of life (QoL) in elderly advanced NSCLC patients, and research on tolerability and toxicity profiles of chemotherapies in this population is similarly limited (Jang et al, 2009;Wildiers et al, 2013). Evidence, however, exists to show that platinum-based doublet chemotherapy is preferable to single-agent therapy for elderly, advanced NSCLC patients with good performance status who are likely to tolerate such therapy (Quoix et al, 2011;Qi et al, 2012). "
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    • "Thus, a large proportion of patients are denied the benefit of aggressive treatment. Moreover, many of the prospective clinical trials have excluded this group of patients from the trials, and thus, no worthwhile clinical studies were forthcoming from this age group, especially in developing countries [6] [7]. Therefore, there seems to be a need to integrate and optimize treatment planning for elderly cancer patients to achieve an improved tumor control, quality of life, and survival with better health care [5] [8]-[10]. "
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