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Assessing Correlation between Surrogate Endpoints and Overall Survival for Oncology Clinical Trials
Guotao Chu1, Xiaochen Zhu1, Jiaju Wu1
1Global Biometrics & Data Sciences, Bristol Myers Squibb, Princeton, New Jersey, USA.
Clinical Pharmacology and Therapeutics
|February 27, 2025
Summary
Progression-free survival (PFS) is a more reliable surrogate endpoint than objective response rate (ORR) for overall survival (OS) in cancer trials. Immune-oncology therapies and first-line treatments show stronger correlations.
Area of Science:
- Oncology
- Clinical Trials
- Biostatistics
Background:
- Surrogate endpoints like PFS and ORR accelerate oncology drug development.
- Their effectiveness in predicting overall survival (OS) requires rigorous validation.
- An integrated dataset from Bristol Myers Squibb was utilized for comprehensive analysis.
Purpose of the Study:
- To evaluate the correlation between surrogate endpoints (PFS, ORR) and OS.
- To assess endpoint reliability across diverse cancer types, treatments, and therapy lines.
- To compare patient-level and trial-level correlations for surrogate endpoint validation.
Main Methods:
- Analysis of an integrated dataset from Bristol Myers Squibb.
- Correlation assessment between PFS, ORR, and OS at patient and trial levels.
- Examination of correlations across different cancer types, treatments (chemotherapy vs. IO), and therapy lines (first-line vs. later lines).
Main Results:
- Patient-level: PFS showed a stronger correlation with OS than best overall response (BOR).
- Melanoma patients had the highest OS-BOR correlation; IO therapy patients showed stronger correlations than chemotherapy.
- First-line therapy patients exhibited stronger correlations between BOR, PFS, and OS compared to later lines.
- Trial-level: PFS hazard ratio (HR) and ORR difference (∆ORR) showed the strongest correlation.
- Melanoma and IO therapy studies demonstrated consistent and significant correlations.
Conclusions:
- PFS appears to be a more reliable surrogate endpoint for OS than BOR in oncology trials.
- Correlations are influenced by cancer type, treatment modality (IO vs. chemotherapy), and therapy line.
- Trial-level analysis of PFS HR and ∆ORR provides robust validation for surrogate endpoint effectiveness.
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