Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune Checkpoint Inhibitors for Advanced Solid Cancers: A Systematic Review and Meta-analysis

JAMA Oncology
Georgia RitchieChee Khoon Lee

Abstract

Checkpoint inhibitors have a unique mechanism of action that differs from chemotherapy or targeted therapies. The validity of objective response rate (ORR) as a surrogate for progression-free survival (PFS) and overall survival (OS) in checkpoint-inhibitor trials is uncertain. To determine the types of primary end points used in phase 2 checkpoint-inhibitor trials, and to assess the strength of associations for ORR with PFS and OS. Trials listed in electronic databases from 2000 to 2017 (PREMEDLINE, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials). Advanced solid cancers in phase 2 and phase 3 trials. Correlations between ORR odds ratios and hazard ratios (HRs) for PFS and OS were examined for randomized comparisons. Within checkpoint-inhibitor treatment arms, correlations for ORR with 6-month PFS and 12-month OS rates were examined. All analyses were weighted by trial size. Multivariable models to predict 6-month PFS and 12-month OS rates from ORR were developed and their performance validated in an independent sample of trials. Correlation coefficient (r) of ORR with PFS and OS. Of 87 phase 2 trials identified, ORR was the most common (52 [60%]) primary end point. Twenty randomized clinical trials with...Continue Reading

Citations

Jun 16, 2018·Journal of Clinical Medicine·Megan B BarnetSteven Kao
Dec 12, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ravi B Parikh, Vinay Prasad
Feb 28, 2020·JAMA : the Journal of the American Medical Association·David L DeMetsThomas R Fleming
Apr 3, 2020·Journal for Immunotherapy of Cancer·Luca MazzarellaGiuseppe Curigliano
Jul 11, 2020·Cancer Immunology, Immunotherapy : CII·Eiki IchiharaKatsuyuki Kiura
Aug 28, 2020·Statistics in Medicine·Huaqing Jin, Guosheng Yin
May 21, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Josep M LlovetUNKNOWN AASLD Panel of Experts on Trial Design in HCC
Apr 1, 2020·American Society of Clinical Oncology Educational Book·Andrew D SeidmanJulia A Beaver
Oct 18, 2019·Immunotherapy·Elissar MoujaessHampig Raphael Kourie
Feb 10, 2021·Journal for Immunotherapy of Cancer·Thomas KelleherDominic F Labriola
Mar 9, 2021·Der Urologe. Ausg. A·G Niegisch, T S Worst
May 18, 2019·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Sandra AssounGérard Zalcman
Apr 20, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sergey TjulandinIvan Kuryshev
Jun 16, 2021·Value in Health Regional Issues·Yesenia OrtizEsteban Hernández

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