Shi Q, et al. - In this large pooled analysis of individual patient data, progression-free survival (PFS) and PFS at 24 months (PFS24) were evaluated as surrogate endpoints for overall survival (OS) in first-line diffuse large B-cell lymphoma (DLBCL). Findings support PFS as a surrogate end point for OS in future randomized controlled trials assessing chemoimmunotherapy in DLBCL. Using this endpoint may accelerate therapeutic development so novel therapies can be brought to these patients years before OS results are mature.

Methods

• Researchers performed analysis of individual patient data from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS.
• Using both linear regression (R² _WLS) and Copula bivariable (R² _Copula) models, they evaluated trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS.
• For surrogacy, prespecified criteria required either R²_WLS or R² _Copula ≥ 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60.

Results

• Findings revealed strong trial-level surrogacy for PFS (R²_WLS = 0.83; R² _Copula = 0.85); it met the predefined criteria for surrogacy.
• PFS was noted to have strong correlation with OS at the patient level.
• The surrogate threshold effect displayed a hazard ratio of 0.89.
• Across comparisons with or without rituximab and with rituximab maintenance trials, surrogacy remained consistent.
• Relatively strong trial-level surrogacy for PFS24 was noted (R² _WLS = 0.77; R² _Copula = 0.78) but it did not meet prespecified criteria.
• PFS24 was noted to have significant correlation with OS at the patient level.
• The surrogate threshold effect displayed an odds ratio of 1.51.