Evaluation of the True Endpoint of Clinical Trials for Cancer Cachexia

Cachexia is an old disease but a new research area that has recently been vigorously investigated. The diagnostic and staging criteria for cancer-associated cachexia have been established through an international consensus report (CR) published in 2011, which may greatly influence the designs and interventions of future clinical trials. However, no standard treatment has been established so far. This may be partially due to the lack of a widely accepted common endpoint for clinical trials. This review aimed to summarize designs and endpoints of 65 randomized controlled trials for cancer cachexia in the past 16 years and seek clinically relevant patient-centered outcomes for future clinical trials. Compared with trials before the CR, trials after the report revealed that the study populations tended to be at the earlier stage of cachexia and included patients with precachexia or those at risk for cachexia. Nonpharmacological interventions have been widely tested, and functional endpoints have increasingly been selected in combination with standard endpoints of body mass or lean body mass. Disability-free survival has recently been used as a functional endpoint in clinical trials in several research fields. It might be also a suitable patient-centered outcome responsive to multiple physical changes in cancer cachexia, and patients might find it more acceptable than other classical endpoints. More efforts would be needed to identify an optimal measurable endpoint and establish a better combination of pharmacological and nonpharmacological interventions to improve the functional prognosis for patients with cancer cachexia. Cachexia is an old disease but a new research area that has recently been vigorously investigated. The diagnostic and staging criteria for cancer-associated cachexia have been established through an international consensus report (CR) published in 2011, which may greatly influence the designs and interventions of future clinical trials. However, no standard treatment has been established so far. This may be partially due to the lack of a widely accepted common endpoint for clinical trials. This review aimed to summarize designs and endpoints of 65 randomized controlled trials for cancer cachexia in the past 16 years and seek clinically relevant patient-centered outcomes for future clinical trials. Compared with trials before the CR, trials after the report revealed that the study populations tended to be at the earlier stage of cachexia and included patients with precachexia or those at risk for cachexia. Nonpharmacological interventions have been widely tested, and functional endpoints have increasingly been selected in combination with standard endpoints of body mass or lean body mass. Disability-free survival has recently been used as a functional endpoint in clinical trials in several research fields. It might be also a suitable patient-centered outcome responsive to multiple physical changes in cancer cachexia, and patients might find it more acceptable than other classical endpoints. More efforts would be needed to identify an optimal measurable endpoint and establish a better combination of pharmacological and nonpharmacological interventions to improve the functional prognosis for patients with cancer cachexia.