Related Experiment Video
Updated: Sep 11, 2026
Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
Treatment Effect Discrepancy Between PFS and OS in Antibody-Drug Conjugate Trials for Metastatic Breast Cancer: A
Luiz Felipe Costa de Almeida1, Anelise Poluboiarinov Cappellaro2, Mariana Macambira Noronha3
1Department of Medical Sciences, Federal Fluminense University, Rio de Janeiro, Brazil.
Objective:
The validity of progression-free survival (PFS) as a surrogate for overall survival (OS) in the antibody-drug conjugate (ADCs) era remains uncertain. We evaluated the association between treatment effects on PFS and OS in randomized trials of ADCs for metastatic breast cancer (mBC) and explored the surrogate threshold effect (STE).
Methods:
PubMed, Embase, Cochrane, and ClinicalTrials.gov were searched for published randomized controlled phase II-IV trials evaluating ADCs in mBC and reporting hazard ratios (HRs) for both PFS and OS. A meta-epidemiological approach was used. The primary metric was the ratio of hazard ratios (rHR = HR_PFS/ HR_OS), with rHR < 1 indicating a larger effect on PFS. Trial-level associations were assessed using weighted linear regression (R²) and Spearman's correlation.
Results:
Twenty-one trials (n = 21; 18 phase III) evaluating nine ADCs were included. The pooled rHR was 0.79 (95% CI, 0.73-0.86), indicating a larger relative effect on PFS than OS. Numerically, the largest discrepancies were observed in triple-negative disease (rHR 0.72) and trials allowing crossover (rHR 0.71). Concordant statistical significance between endpoints occurred in 76% of the trials, whereas 24% showed a significant PFS benefit without OS improvement. The trial-level association between PFS and OS was moderate (R² = 0.62; ρ = 0.67).
Conclusion:
Treatment effects on PFS consistently exceeded those on OS, although effect directions were highly concordant between endpoints. These findings provide an exploratory framework to contextualize the relationship between PFS and OS in ADC trials, requiring further validation in diverse clinical settings.
