Correlation between progression-free and overall survival in patients with Hodgkin lymphoma: a comprehensive analysis of individual patient data from randomized German Hodgkin Study Group (GHSG) trials

Abstract

Background: This study aimed to evaluate the correlation between progression-free (PFS) and overall survival (OS) after first-line treatment of classical Hodgkin lymphoma (HL) and to assess the potential of PFS as a surrogate parameter for OS.

Patients and methods: We analyzed individual patient data collected during and after treatment with polychemotherapy in nine randomized phase III trials [German Hodgkin Study Group (GHSG) HD7-HD15] between January 1993 and August 2018. The effects of 16 experimental treatments on PFS and OS at the trial level were evaluated using Cox proportional hazards (PH) regression and linear weighted least squares regression. At the patient level, marginal Cox PH models for multiple endpoints were applied using the Wei-Lin-Weissfeld method.

Results: At least one PFS and OS event was recorded in 1682 and 1064 of 10 605 patients, respectively. At the trial level, there was a strong correlation between treatment effects on PFS and OS (weighted Pearson r = 0.72, R² = 0.54, P < 0.001). At the patient level, a moderate to strong correlation between treatment effects on PFS and OS was observed, with Pearson r values ranging between 0.61 and 0.85 (each P < 0.001) and an overall r = 0.74. A regression model that accounted for different types of experimental treatments and historical progress across trial generations achieved a very strong correlation (R² = 0.93). When applied to data from the contemporary first-line ECHELON-1 trial, this model successfully predicted OS from PFS {prognosticated ln[HR(OS)] = -0.68 as compared with observed ln[HR(0.59)] = -0.53}.

Conclusion: In first-line trials of HL, PFS and OS, as well as treatment effects and prognostic effects on these endpoints, are strongly correlated. PFS serves as a strong predictor of treatment effects on OS, providing valuable insights many years before OS can be reliably assessed.

Keywords: Hodgkin lymphoma; correlation; overall survival; progression-free survival.