Rethinking end-points for bone-targeted therapy in advanced cancer.
The principal objective for any medical therapy is to improve either the duration of life and/or its quality. Metastases in bone can lead to clinically defined events termed skeletal-related events (SREs) which are a quantifiable measure of skeletal morbidity. Avoidance and/or delay of SREs have become the principal objective in trials exploring the efficacy of bone-targeted therapy in patients with skeletal metastases. Despite reductions in the frequency or rate of SRE occurrence, trials of bone-targeted therapy have failed to show any effect on either progression-free or overall survival when compared with placebo or other bone-targeting agents. Similarly, trials of bone-targeted therapy have not shown consistent effects on quality of life. The validity of SRE-based primary outcome measures in cancer clinical trials is therefore, questionable. More novel end-point selection for trials of bone-targeted therapy seems warranted. Composite measures comprising occurrence of symptomatic skeletal events and patient reported outcomes may be an effective solution and warrants further investigation.
Department of Medical Oncology, Hospital Álvaro Cunqueiro- Estructura Organizativa de Xestión Integrada (EOXI) of Vigo, Spain.
Susana
S
Gómez García
Division of Medical Oncology, The Ottawa Hospital, and University of Ottawa, Ottawa, Canada.
Mark
M
Clemons
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada. Electronic address: eitan.amir@uhn.ca.
Eitan
E
Amir
D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary*; D000069448:Denosumab / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D011788:Quality of Life; D012044:Regression Analysis; D016019:Survival Analysis
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab
Bisphosphonates; Bone metastases; Clinical trials; Denosumab; End-points; Solid tumours