Marion Savina1, Sophie Gourgou2, Antoine Italiano3, Derek Dinart4, Virginie Rondeau5, Nicolas Penel6, Simone Mathoulin-Pelissier7, Carine Bellera8. 1. Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne, 33000 Bordeaux, France; INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux, France; INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France; University of Bordeaux, ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France. Electronic address: marion.savina@u-bordeaux.fr. 2. Biometrics Unit, Institut du Cancer de Montpellier, Comprehensive Cancer Center, 208 Avenue des Apothicaires, 34298 Montpellier, France. Electronic address: sophie.gourgou@icm.unicancer.fr. 3. Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne, 33000 Bordeaux, France; Oncogenesis and Therapeutic Targeting of the Sarcoma Cell, ACTION, INSERM U1218, University of Bordeaux, 33000 Bordeaux, France. Electronic address: A.Italiano@bordeaux.unicancer.fr. 4. Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne, 33000 Bordeaux, France. Electronic address: d.dinart@bordeaux.unicancer.fr. 5. INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France. Electronic address: virginie.rondeau@u-bordeaux.fr. 6. Department of Medical Oncology, Centre Oscar Lambret, Comprehensive Cancer Center, 3 Rue Frédéric Combemale, 59000 Lille, France. Electronic address: n-penel@o-lambret.fr. 7. Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne, 33000 Bordeaux, France; INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux, France; INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France; University of Bordeaux, ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France. Electronic address: S.Mathoulin@bordeaux.unicancer.fr. 8. Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne, 33000 Bordeaux, France; INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux, France; INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France; University of Bordeaux, ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, 146 Rue Léo Saignat, 33076 Bordeaux, France. Electronic address: C.Bellera@bordeaux.unicancer.fr.
Abstract
BACKGROUND: In cancer randomized controlled trials (RCT), alternative endpoints are increasingly being used in place of overall survival (OS) to reduce sample size, duration and cost of trials. It is necessary to ensure that these endpoints are valid surrogates for OS. Our aim was to identify meta-analyses that evaluated surrogate endpoints for OS and assess the strength of evidence for each meta-analysis (MA). MATERIALS AND METHODS: We performed a systematic review to identify MA of cancer RCTs assessing surrogate endpoints for OS. We evaluated the strength of the association between the endpoints based on (i) the German Institute of Quality and Efficiency in Health Care guidelines and (ii) the Biomarker-Surrogate Evaluation Schema. RESULTS: Fifty-three publications reported on 164 MA, with heterogeneous statistical methods Disease-free survival (DFS) and progression-free survival (PFS) showed good surrogacy properties for OS in colorectal, lung and head and neck cancers. DFS was highly correlated to OS in gastric cancer. CONCLUSION(S): The statistical methodology used to evaluate surrogate endpoints requires consistency in order to facilitate the accurate interpretation of the results. Despite the limited number of clinical settings with validated surrogate endpoints for OS, there is evidence of good surrogacy for DFS and PFS in tumor types that account for a large proportion of cancer cases.
BACKGROUND: In cancer randomized controlled trials (RCT), alternative endpoints are increasingly being used in place of overall survival (OS) to reduce sample size, duration and cost of trials. It is necessary to ensure that these endpoints are valid surrogates for OS. Our aim was to identify meta-analyses that evaluated surrogate endpoints for OS and assess the strength of evidence for each meta-analysis (MA). MATERIALS AND METHODS: We performed a systematic review to identify MA of cancer RCTs assessing surrogate endpoints for OS. We evaluated the strength of the association between the endpoints based on (i) the German Institute of Quality and Efficiency in Health Care guidelines and (ii) the Biomarker-Surrogate Evaluation Schema. RESULTS: Fifty-three publications reported on 164 MA, with heterogeneous statistical methods Disease-free survival (DFS) and progression-free survival (PFS) showed good surrogacy properties for OS in colorectal, lung and head and neck cancers. DFS was highly correlated to OS in gastric cancer. CONCLUSION(S): The statistical methodology used to evaluate surrogate endpoints requires consistency in order to facilitate the accurate interpretation of the results. Despite the limited number of clinical settings with validated surrogate endpoints for OS, there is evidence of good surrogacy for DFS and PFS in tumor types that account for a large proportion of cancer cases.
Authors: Devon J Boyne; Colleen A Cuthbert; Dylan E O'Sullivan; Tolulope T Sajobi; Robert J Hilsden; Christine M Friedenreich; Winson Y Cheung; Darren R Brenner Journal: JAMA Netw Open Date: 2019-05-03
Authors: Wanling Xie; Susan Halabi; Jayne F Tierney; Matthew R Sydes; Laurence Collette; James J Dignam; Marc Buyse; Christopher J Sweeney; Meredith M Regan Journal: JNCI Cancer Spectr Date: 2019-02-06