Disease-free survival as a surrogate for overall survival in HR+/HER2– early breast cancer: A correlation analysis
Untch M, Pérol D, Mayer EL, Cortes J, Nusch A, Cameron D, Barrios C, Delea T, Danyliv A, Mishra N, Gupta R, Pathak P, Fasching P (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 202
Article Number: 113977
DOI: 10.1016/j.ejca.2024.113977
Abstract
Background: Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival (DFS) has been widely adopted as a primary endpoint for early breast cancer (EBC) trials, as follow-up is comparatively shorter. Here, we present an analysis evaluating DFS as a surrogate for OS for adjuvant treatment of hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) EBC. Methods: A systematic literature review which included randomized controlled trials (RCTs) with ≥80% of adult patients with HR+/HER2– EBC was conducted. The RCTs evaluated various systemic therapeutic categories; key inclusion criteria included reporting of DFS and OS hazard ratios (HRs) and mature OS data. Spearman rank correlation and weighted linear regression analyses evaluated DFS and OS HR correlation. A scenario analysis tested base-case analysis robustness, and a parallel analysis using patient-level data was conducted. Results: The base case (N = 14 RCTs) showed an unweighted Spearman coefficient of 0.81 between OS and DFS (weighted: 0.81), with 84% of the variability in OS explained by DFS differences (R2 from weighted regression). The surrogate threshold effect (Burzykowski T, Buyse M. Pharm Stat. 2006;5:173–186) was 0.82 for DFS/OS HR. Scenario analysis (n = 9 RCTs), which excluded chemotherapy trials, and patient-level analysis using FACE trial data were consistent with the base-case analysis. Conclusions: These analyses support DFS as a reliable surrogate endpoint for OS in adjuvant HR+/HER2− EBC trials. Using DFS as a surrogate measure will permit timelier access to novel treatments for patients with HR+/HER2− EBC.
Authors with CRIS profile
Involved external institutions
HELIOS Kliniken
Germany (DE)
Centre Léon-Bérard (UNICANCER)
France (FR)
Novartis India
India (IN)
Dana–Farber Cancer Institute
United States (USA) (US)
Novartis AG
Switzerland (CH)
International Breast Cancer Centre (IBCC)
Spain (ES)
University of Edinburgh
United Kingdom (GB)
LACOG - Latin American Cooperative Oncology Group
Brazil (BR)
Policy Analysis Inc (PAI)
United States (USA) (US)
Germany (DE)
Centre Léon-Bérard (UNICANCER)
France (FR)
Novartis India
India (IN)
Dana–Farber Cancer Institute
United States (USA) (US)
Novartis AG
Switzerland (CH)
International Breast Cancer Centre (IBCC)
Spain (ES)
University of Edinburgh
United Kingdom (GB)
LACOG - Latin American Cooperative Oncology Group
Brazil (BR)
Policy Analysis Inc (PAI)
United States (USA) (US)
How to cite
APA:
Untch, M., Pérol, D., Mayer, E.L., Cortes, J., Nusch, A., Cameron, D.,... Fasching, P. (2024). Disease-free survival as a surrogate for overall survival in HR+/HER2– early breast cancer: A correlation analysis. European Journal of Cancer, 202. https://doi.org/10.1016/j.ejca.2024.113977
MLA:
Untch, Michael, et al. "Disease-free survival as a surrogate for overall survival in HR+/HER2– early breast cancer: A correlation analysis." European Journal of Cancer 202 (2024).
BibTeX: Download