Correlation Between Progression-Free and Overall Survival in Patients with Hodgkin Lymphoma: A Comprehensive Analysis of Individual Patient Data from Randomized GHSG Trials

We aimed to evaluate the correlation of progression-free (PFS) and overall survival (OS) after first-line treatment of classical Hodgkin lymphoma (HL) and the potential of PFS to serve as a surrogate parameter for OS. We analyzed individual patient data obtained during and after treatment with polychemotherapy within nine randomized phase III trials (GHSG HD7-HD15) between 01/93 - 08/18. Effects of 16 experimental treatments on PFS and OS on trial level were evaluated by estimation of the treatment effects with Cox proportional hazards (PH) regression and a linear weighted least squares regression. On the patient level, marginal Cox PH models for multiple endpoints were applied according to the Wei-Lin-Weissfeld method. At least one PFS and OS event was recorded in 1,682 and 1,064 of 10,605 patients, respectively. At trial level there was a strong correlation of treatment effects on PFS and OS (weighted Pearson r= 0.72, R2= 0.54, P< 0.001). At patient level, moderate to strong correlation of treatment effects on PFS and OS was confirmed with Pearson r ranging between 0.61 - 0.85 (each P< 0.001) and overall r= 0.74. A regression model accounting for different types of experimental treatments and historical progress over trial generations reached very strong correlation (R2= 0.93). Applying this model to data from the contemporary first-line ECHELON-1 trial allowed for prediction of OS from PFS (prognosticated ln[HR(OS)]= -0.68 as compared to observed ln[HR(0.59)]= -0.53). In first-line trials of HL, PFS and OS as well as treatment effects and prognostic effects on PFS and OS are strongly correlated. PFS thereby predicts treatment effects on OS to a high degree and many years before OS can be reliably evaluated.