Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in...

Area of Science:

• Oncology
• Clinical Trials
• Biostatistics

Background:

• Disease-free survival (DFS) is commonly used as a primary endpoint in early breast cancer trials.
• Its validation as a surrogate for overall survival (OS) in the context of anti-HER2 antibody treatment remains crucial.
• This study addresses the surrogacy of DFS for OS in HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy.

Purpose of the Study:

• To investigate the validity of disease-free survival as a surrogate endpoint for overall survival.
• To assess the patient-level and trial-level correlations between DFS and OS.
• To determine the surrogate threshold effect for anti-HER2 antibody trials in early breast cancer.

Main Methods:

• A systematic review and meta-analysis of randomized controlled trials (RCTs) involving anti-HER2 antibodies in early breast cancer.
• Inclusion criteria: completed accrual, available DFS and OS data, adjuvant anti-HER2 antibody treatment.
• Statistical analysis included Spearman's correlation (r_s) for patient-level association and R² for trial-level association of hazard ratios.

Main Results:

• Strong patient-level association between DFS and OS (r_s=0·90).
• Trial-level analysis showed R²=0·75, indicating a robust relationship between DFS and OS hazard ratios.
• Surrogate threshold effects ranged from 0·56 to 0·81, depending on the expected number of deaths.

Conclusions:

• Disease-free survival is an appropriate surrogate for overall survival in HER2-positive early breast cancer trials.
• The findings support the continued use of DFS as a primary endpoint in this setting.
• A key limitation is the study's reliance on the included trials and a potential outlying trial.