TY - JOUR
T1 - PET-CR as a potential surrogate endpoint in untreated DLBCL
T2 - meta-analysis and implications for clinical trial design
AU - Broglio, Kristine
AU - Kostakoglu, Lale
AU - Ward, Carol
AU - Mattiello, Federico
AU - Sahin, Denis
AU - Nielsen, Tina
AU - McGlothlin, Anna
AU - Elliott, Corrine F.
AU - Witzig, Thomas
AU - Sehn, Laurie H.
AU - Trnĕný, Marek
AU - Vitolo, Umberto
AU - Martelli, Maurizio
AU - Foster, Margaret
AU - Wendelberger, Barbara
AU - Nowakowski, Grzegorz
AU - Berry, Donald A.
N1 - Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Bayesian hierarchical model
KW - clinical trial simulation
KW - diffuse large B-cell lymphoma
KW - end-of-treatment PET-complete response
KW - meta-analysis
KW - progression-free and overall survival
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UR - http://www.scopus.com/inward/citedby.url?scp=85133717894&partnerID=8YFLogxK
U2 - 10.1080/10428194.2022.2095624
DO - 10.1080/10428194.2022.2095624
M3 - Article
C2 - 35815677
AN - SCOPUS:85133717894
SN - 1042-8194
VL - 63
SP - 2816
EP - 2831
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 12
ER -