Dataset Information

Surrogate Endpoints as Predictors of Overall Survival in Metastatic Urothelial Cancer: A Trial-level Analysis.

ABSTRACT:

Background

Surrogate endpoints (SEs), such as progression-free survival (PFS) and objective response rate (ORR), are frequently used in clinical trials. The relationship between SEs and overall survival (OS) has not been well described in metastatic urothelial cancer (MUC).

Objective

We evaluated trial-level data to assess the relationship between SEs and OS. We hypothesize a moderate surrogacy relationship between both PFS and ORR with OS.

Design setting and participants

We systematically reviewed phase 2/3 trials in MUC with two or more treatment arms, and report PFS and/or ORR, and OS.

Outcome measurements and statistical analysis

Linear regression was performed, and the coefficient of determination (R²) and surrogate threshold effect (STE) estimate were determined between PFS/ORR and OS.

Results and limitations

Of 3791 search results, 59 trials and 62 comparisons met the inclusion criteria. Of the 53 trials that reported PFS, 31 (58%) reported proportional hazard regression for PFS and OS. Linear regression across trials demonstrated an R² of 0.60 between hazard ratio (HR) for PFS (HR^PFS) and HR for OS (HR^OS), and an STE of 0.41. Linear regression of ΔPFS (median PFS in months of the treatment arm - that of the control arm) and ΔOS demonstrated an R² of 0.12 and an STE of 14.1 mo. Thirty trials reported ORRs. Linear regression for ORR^ratio and HR^OS among all trials found an R² of 0.08; an STE of 95% was not reached at any value and ΔORR and HR^OS similarly demonstrated a poor correlation with an R² value of 0.03.

Conclusions

PFS provides only a moderate level of surrogacy for OS; An HR^PFS of ≤0.41 provides 95% confidence of OS improvement. ORR is weakly correlated with OS and should be de-emphasized in MUC clinical trials. When PFS is discussed, proportional hazard regression should be reported.

Patient summary

We examined the relationship between surrogate endpoints, common outcomes in clinical trials, with survival in urothelial cancer trials. Progression-free survival is moderately correlated, while objective response rate had a poor correlation with survival and should be de-emphasized as a primary endpoint.

SUBMITTER: Ghali F

PROVIDER: S-EPMC9806712 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Surrogate Endpoints as Predictors of Overall Survival in Metastatic Urothelial Cancer: A Trial-level Analysis.

Ghali Fady F Zhao Yibai Y Patel Devin D Jewell Teresa T Yu Evan Y EY Grivas Petros P Montgomery R Bruce RB Gore John L JL Etzioni Ruth B RB Wright Jonathan L JL

European urology open science 20221215

<h4>Background</h4>Surrogate endpoints (SEs), such as progression-free survival (PFS) and objective response rate (ORR), are frequently used in clinical trials. The relationship between SEs and overall survival (OS) has not been well described in metastatic urothelial cancer (MUC).<h4>Objective</h4>We evaluated trial-level data to assess the relationship between SEs and OS. We hypothesize a moderate surrogacy relationship between both PFS and ORR with OS.<h4>Design setting and participants</h4>W ...[more]

PMID: 36601043

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Dataset Information

Surrogate Endpoints as Predictors of Overall Survival in Metastatic Urothelial Cancer: A Trial-level Analysis.

Background

Objective

Design setting and participants

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Publications

Surrogate Endpoints as Predictors of Overall Survival in Metastatic Urothelial Cancer: A Trial-level Analysis.

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