Sébastien Branchoux1, Carine Bellera2, Antoine Italiano3, Denis Rustand4, Anne-Françoise Gaudin5, Virginie Rondeau6. 1. Department of Health Economics & Outcomes Research, Bristol-Myers Squibb, Rueil-Malmaison, France; Biostatistic Team, Bordeaux Population Health Center, ISPED, Centre INSERM U1219, INSERM, Bordeaux, France; Epicene Team (Cancer & Environnement), Bordeaux Population Health Center, ISPED, Centre INSERM U1219, INSERM, Bordeaux, France. Electronic address: Sebastien.branchoux@bms.com. 2. Epicene Team (Cancer & Environnement), Bordeaux Population Health Center, ISPED, Centre INSERM U1219, INSERM, Bordeaux, France; Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France; Department of Clinical Epidemiology, INSERM CIC-EC 14.01, Bordeaux, France. 3. Department of Early Phase Trial Unit, Institut Bergonié Comprehensive Cancer Centre, Bordeaux, France. 4. Biostatistic Team, Bordeaux Population Health Center, ISPED, Centre INSERM U1219, INSERM, Bordeaux, France. 5. Department of Health Economics & Outcomes Research, Bristol-Myers Squibb, Rueil-Malmaison, France. 6. Biostatistic Team, Bordeaux Population Health Center, ISPED, Centre INSERM U1219, INSERM, Bordeaux, France; Epicene Team (Cancer & Environnement), Bordeaux Population Health Center, ISPED, Centre INSERM U1219, INSERM, Bordeaux, France.
Abstract
BACKGROUND: Surrogate endpoints (SEs) for overall survival (OS) are specific to therapeutic class. The objective of this review was to document all alternative endpoints studied for their association with OS in Immune-Checkpoint Inhibitors (ICI)-treated patients. METHODS: We searched PubMed and Embase for publications reporting the association between a clinical endpoint and OS in ICI-treated populations from 01/01/2003 to 03/31/2018. RESULTS: Out of 6,335 references identified, 24 were selected. Only 3 studies assessed surrogacy at both the patient and trial levels. The main traditional alternative endpoints included progression-free survival (N = 10) and objective response rate (N = 8). New alternative endpoints, such as durable response rate (N = 1) and intermediate response endpoint (N = 1) statistically better correlate with OS in the cancer types analysed. CONCLUSION: Based on the published evidence, there is insufficient data to support validated SE for OS. Adequate surrogacy assessment of promising composite endpoints which consider a duration component is encouraged.
BACKGROUND: Surrogate endpoints (SEs) for overall survival (OS) are specific to therapeutic class. The objective of this review was to document all alternative endpoints studied for their association with OS in Immune-Checkpoint Inhibitors (ICI)-treated patients. METHODS: We searched PubMed and Embase for publications reporting the association between a clinical endpoint and OS in ICI-treated populations from 01/01/2003 to 03/31/2018. RESULTS: Out of 6,335 references identified, 24 were selected. Only 3 studies assessed surrogacy at both the patient and trial levels. The main traditional alternative endpoints included progression-free survival (N = 10) and objective response rate (N = 8). New alternative endpoints, such as durable response rate (N = 1) and intermediate response endpoint (N = 1) statistically better correlate with OS in the cancer types analysed. CONCLUSION: Based on the published evidence, there is insufficient data to support validated SE for OS. Adequate surrogacy assessment of promising composite endpoints which consider a duration component is encouraged.
Authors: Casey Quinn; Louis P Garrison; Anja K Pownell; Michael B Atkins; Gérard de Pouvourville; Kevin Harrington; Paolo Antonio Ascierto; Phil McEwan; Samuel Wagner; John Borrill; Elise Wu Journal: J Immunother Cancer Date: 2020-07 Impact factor: 13.751