PROs vs clinician-reported adverse events in a large clinical trial: findings from the phase 3 POLARIX study
Abstract
Abstract Diffuse large B-cell lymphoma (DLBCL) poses a challenge in hematology given its varied symptoms, and the complex interplay between disease and treatment effects on health-related quality of life (HRQoL). The phase 3 POLARIX study demonstrated superior progression-free survival and a similar safety profile with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with previously untreated DLBCL. Here, we evaluate HRQoL through patient-reported outcome (PRO) instruments to fully characterize the patient experience in the POLARIX study. Changes from baseline in HRQoL, lymphoma symptoms, and gastrointestinal (GI) symptoms were assessed, as well as incidence and severity of common symptoms by PROs vs clinician-reported adverse events (AEs). Baseline characteristics of PRO-evaluable patients (N = 874) were consistent. Comparison between PROs and clinician-reported AEs revealed a notable discordance; patients generally reported a higher incidence of symptoms than clinicians, emphasizing the need for patient-centric tools to accurately capture the patient experience. Both treatments exhibited rapid and sustained improvements in HRQoL and lymphoma symptoms, with the most substantial improvements seen in global health status/QoL, lymphoma symptoms, fatigue, role, emotional, and social functioning. GI symptoms (diarrhea, constipation, nausea, and vomiting) were generally similar between treatment arms and returned to baseline levels after treatment completion. These HRQoL data underscore the complementarity of PROs, as an adjunct to clinician-reported AEs, in evaluating the efficacy and tolerability of new treatments, including Pola-R-CHP, which may represent a new benchmark for patient-reported HRQoL in previously untreated DLBCL. This trial was registered at www.clinicaltrials.gov as NCT03274492.
Article Details
Authors (30)
Carrie Thompson
1Mayo Clinic College of Medicine, Rochester, MN
Marek Trneny
Franck Morschhauser
Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France
Gilles Salles
41Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
Patrick M. Reagan
16University of Rochester Medical Center, Rochester, NY
Mark Hertzberg
Huilai Zhang
Catherine Thieblemont
15Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis, Hémato-Oncologie and Université Paris Cité, Paris, France
Bei Hu
Gustavo Fonseca
Won Seog Kim
Maurizio Martelli
12Hematology Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
Amitkumar Mehta
Avrita Singh
14Genentech, Inc., South San Francisco, CA
Mark Yan
15Hoffmann-La Roche Ltd, Mississauga, ON, Canada
Jamie Hirata
14Genentech, Inc., South San Francisco, CA
Matthew Sugidono
14Genentech, Inc., South San Francisco, CA
Calvin Lee
14Genentech, Inc., South San Francisco, CA
Jeff P. Sharman
1Willamette Valley Cancer Institute, Sarah Cannon Research, Eugene, OR
Neha Mehta-Shah
3Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Christopher R. Flowers
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine
Hervé Tilly
5Service Hématologie, Centre Henri Becquerel, Rouen, France
Neil Chua
20Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
René-Olivier Casasnovas
21Centre Hospitalier Universitaire Dijon Bourgogne, Dijon, France
Fiona Miall
22Department of Hematology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
Tae Min Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
Xavier Cheng-Hong Tsai
24National Taiwan University Hospital, Taipei, Taiwan
Sunita Nasta
25University of Pennsylvania Hospital, Philadelphia, PA
Seung Tae Lee
26Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, MD
Jonathan W. Friedberg
18Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY