- A meta-analysis finds that DFS is strongly or moderately strongly correlated with OS in clinical trials of adjuvant trastuzumab given up to 1 year in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBCa).
Why this matters
- This is the first meta-analysis to validate DFS as a surrogate for OS in eBCa.
- Using DFS as a surrogate should expedite drug development.
- Meta-analysis of 8 clinical trials (n=21,480), after search of bibliographic databases (eg, Medline), clinical trial registries, and trial registries from pharmaceutical companies.
- DFS refers to any type of recurrence (invasive or noninvasive) or death from any cause.
- Patient-level (rs) and trial-level (R2) correlations were calculated between DFS and OS.
- The surrogate threshold effect was the maximum HR for DFS that statistically predicts an HR for OS less than 1.00 in a future trial.
- Funding: Roche Pharma AG.
- Patient-level associations between DFS and OS were strong (rs=0.90; 95% CI, 0.89-0.90).
- Trial-level associations between DFS and OS were moderate to strong (R2, 0.75; 95% CI, 0.50-1.00) in 1 model covering all 8 trials, or strong (R2, 0.84; 95% CI, 0.67-1.00) in a second model covering fewer trials.
- Surrogate threshold effects ranged from 0.56 to 0.81, based on all 8 trials.
- Regression analyses are sensitive to outliers.