Endpoints in clinical trials in cancer cachexia: where to start?

Abstract

Purpose of review:The lack of agreement and knowledge of optimal endpoints in cachexia trials have impeded progress in finding interventions counteracting the devastating effects cancer cachexia has on morbidity and mortality. An endpoint should both be sensitive enough to detect change and specific enough not to be influenced by other conditions or treatments. Recent findings:There is a wealth of potential and applied endpoints in trials investigating cachexia. As of today, there is no generally acknowledged consensus, but assessments of key factors such as body composition should continue to be applied. However, the impact and effect size necessary to achieve clinical benefit using these endpoints are not clear. Further, the use of other endpoints assessing physical function, symptom evaluation and quality of life remains to be elucidated. Summary:It is essential that endpoints are clinically relevant and further research is therefore needed to develop endpoints that are meaningful for patients with cachexia.

Natural ghrelin in advanced cancer patients with cachexia, a case series

“…To reflect the proposed effect of ghrelin on appetite, food intake, muscle, inflammation, and psychological measurements, a multitude of outcomes representing different domains of cancer cachexia were measured, because meaningful outcomes in cancer cachexia research remain a matter of debate 25 . These target outcomes may change along the trajectory of cancer cachexia 26 . In the early stage of cachexia, muscle mass and function are the central focus.…”

Weight loss over time and survival: a landmark analysis of 1000+ prospectively treated and monitored lung cancer patients

“…Indeed, the multifaceted nature of this constellation of signs and symptoms only adds to the quandary of choosing the most appropriate clinical trial eligibility criteria and endpoints. [1][2][3] Not surprisingly, the recent unsuccessful cancer cachexia clinical trials have prompted only further discussion of clinical trial design and choice of appropriate eligibility criteria and endpoints. [4][5][6][7] Simple, unadorned, and inexpensive, weight has, at times, been incorporated into cancer cachexia trials.…”

“…It is a syndrome characterized by weight loss, poor appetite, attrition of both lean tissue and fat but especially the former, an otherwise inexplicable increase in basal metabolic rate, a decline in patient functional status, and poor survival. Indeed, the multifaceted nature of this constellation of signs and symptoms only adds to the quandary of choosing the most appropriate clinical trial eligibility criteria and endpoints 1–3 . Not surprisingly, the recent unsuccessful cancer cachexia clinical trials have prompted only further discussion of clinical trial design and choice of appropriate eligibility criteria and endpoints 4–7 …”

The Relationship between ECOG-PS, mGPS, BMI/WL Grade and Body Composition and Physical Function in Patients with Advanced Cancer

“…The findings of the present study may also help inform regulatory endpoints in the arena of trials treating cancer cachexia. To date there has been a lack of concordance in regulatory guidance between the EMA and FDA regarding endpoints [43] whilst previously agreed endpoints of skeletal muscle mass and function have not been realized in multiple clinical trials of varying agents [44][45][46][47]. It may be that moderating the systemic inflammatory response in patients with advanced cancer will produce more reproducible gains.…”