PET-CR as a potential surrogate endpoint in untreated DLBCL: meta-analysis and implications for clinical trial design.
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This study's focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint.
author list (cited authors)
Broglio, K., Kostakoglu, L., Ward, C., Mattiello, F., Sahin, D., Nielsen, T., ... Berry, D. A.
complete list of authors
Broglio, Kristine||Kostakoglu, Lale||Ward, Carol||Mattiello, Federico||Sahin, Denis||Nielsen, Tina||McGlothlin, Anna||Elliott, Corrine F||Witzig, Thomas||Sehn, Laurie H||Trnĕný, Marek||Vitolo, Umberto||Martelli, Maurizio||Foster, Margaret||Wendelberger, Barbara||Nowakowski, Grzegorz||Berry, Donald A