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

Abstract

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.

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

“…However, the clinical applicability of trial results depends largely on whether the study participants are representative of the population of interest [6]. Consequently, for disease entities for which the majority of patients actually are older patients with comorbidities, including these patients will supply a much more faithful reflection of true clinical benefit [12]. Such trials will allow cancer specialists to make treatment recommendations that apply to their real-life patient populations rather than to highly selected subgroups.…”

The effects of age on health-related quality of life in cancer populations: A pooled analysis of randomized controlled trials using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 involving 6024 cancer patients

“…Another option might be to enroll older patients in smaller "sub-trials" within bigger trials or to design end points specifically for older patients, which could include HRQOL endpoints such as physical functioning which are equally important for the elderly than extending survival. 17 However more longitudinal and observational studies, with no stringent inclusion criteria, are needed to confirm these statements.…”

“…15,16,17 The availability of new molecularly targeted agents and newly improved existing agents has expanded the range of treatments options available for elderly cancer patients. 18 Some of these agents have shown better tolerability and a better safety profile 19 and may therefore provide new options for systemic therapy suitable to the elderly cancer population.…”

Comparison of capecitabine and tegafur/gimeracil/oteracil (S-1) in the treatment of advanced breast carcinoma in the elderly

“…Surgery and chemotherapy are the major treatment methods for breast cancer. To extend survival as much as possible, chemotherapy without surgical treatment is more appropriate for late-stage breast cancer [3,4]. The most preferred chemotherapeutic drugs are anthracyclines and taxanes, but their toxicity and side effects can severely reduce treatment effectiveness andquality of life for elderly patients most such patients are intolerant of combined chemotherapy.…”