Abstract
Correlation analysis to assess surrogate endpoints for overall survival (OS) in triple-negative breast cancer (TNBC).
Author
person
Judith Pérez-Granado
The Larvol Group, LLC, San Francisco, CA
info_outline
Judith Pérez-Granado, Ankit Kalucha, Kinisha Gala, Olga Bodriagova, Laura Vidal, Bruno Larvol, Mark Gramling, Kamal S. Saini
Full text
Authors
person
Judith Pérez-Granado
The Larvol Group, LLC, San Francisco, CA
info_outline
Judith Pérez-Granado, Ankit Kalucha, Kinisha Gala, Olga Bodriagova, Laura Vidal, Bruno Larvol, Mark Gramling, Kamal S. Saini
Organizations
The Larvol Group, LLC, San Francisco, CA, LabCorp Drug Development, Princeton, NJ, Labcorp Drug Development, Burlington, NC, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
Abstract Disclosures
Research Funding
No funding received
None.
Background:
The use of surrogate endpoints can help reduce the trial duration and cost which is important for aggressive diseases such as TNBC. Previous studies suggest progression-free survival (PFS) may serve as a surrogate for OS in metastatic TNBC. We aim to evaluate PFS and additional surrogate endpoints for their correlation with OS in localized and advanced TNBC.
Methods:
TNBC phase 3 trials and pooled analysis as well as trials including TNBC subgroups, were identified through a systematic search using LARVOL CLIN, PubMed, clinicaltrials.gov, and conference proceedings. Out of these, trials reporting median survival and hazard ratios (HR) for both OS and surrogate endpoints were considered for further statistical analysis. Surrogate endpoints reported by fewer than 4 trials were excluded from the study. Pearson correlation (r) and determination coefficient (R
2
) were calculated to assess surrogacy between Median OS and Median PFS, HR OS and HR PFS, HR disease-free survival (DFS), and invasive disease-free survival (IDFS). Weighted regression analysis was conducted controlling for sample size among trial arms.
Results:
26 TNBC cohorts and 2 pooled analyses evaluating PARP, PD-1, PD-L1 inhibitors, and chemotherapies were included. The association analysis results are shown. There was a significant correlation between median OS and median PFS (r = 0.73, p value = 1.026×10
−6
) as well as between HR OS and HR PFS (r = 0.61, p value = 0.009). There was also a significant correlation between HR DFS and HR IDFS with HR OS (r = 0.92, p value = 0.003; r = 0.99, p value = 0.014).
Conclusions:
PFS is significantly correlated with OS in TNBC across diverse therapies. Also, HR PFS, HR DFS, and HR IDFS are significantly correlated with HR OS. Overall, these results illustrate that PFS could be used as a surrogate for OS in TNBC. Subsequent studies should include early-phase trials to increase association robustness and enable correlation comparison between the diverse mechanism of actions and other surrogate endpoints.
Statistical analysis of outcome and trial surrogacy.
Number of Trials
Pearson correlation coefficient, r
(p-value)
Determination coefficient, R
2
Weighted regression slope
(SE; p-value)
Median OS - Median PFS
17
1
0.73 (1.026×10
−6
)
0.53
1.62 (0.2; < 0.001)
HR OS - HR PFS
17
1
0.61 (0.009)
0.37
0.26 (0.12; < 0.01)
HR OS - HR DFS
7
0.92 (0.003)
0.84
1.38 (0.21; < 0.001)
HR OS - HR IDFS
4
0.99 (0.014)
0.97
1.25 (0.14; < 0.01)
1
Includes 15 trials and 2 pooled analyses studies. SE = standard error.
3 organizations
4 drugs
3 targets
Organization
The Larvol Group, LLCOrganization
Labcorp Drug Development Inc., Princeton, NJDrug
PARP inhibitorsDrug
PD-1 inhibitorsDrug
PD-L1 inhibitorsDrug
chemotherapiesTarget
PD-L1Target
PD-1Target
PARP