Effect Sizes Hypothesized and Observed in Contemporary Phase III Trials of Targeted and Immunological Therapies for Advanced Cancer

JNCI Cancer Spectrum
Nicola Jane LawrenceMartin R Stockler

Abstract

We sought to compare the effect sizes hypothesized in the trial design, observed in the trial results, and considered clinically meaningful by the American Society of Clinical Oncology (ASCO) 2014 recommendations, in phase III trials of targeted and immunological therapies. We studied phase III, superiority trials of targeted and immunological therapies in advanced cancers published from 2005 to 2015. We recorded the characteristics, design parameters, and observed results for the primary endpoint of each trial. The effect sizes hypothesized in the trial design were compared with the ASCO 2014 recommendation that phase III trials be designed to detect overall survival (OS) benefits that are clinically meaningful (hazard ratio ≤0.8). All critical elements of the trial design (effect sizes hypothesized, estimated survival in the control group, power, and significance level) were identified in 165 of 213 included trials (77%). Of trials with a statistically significant result for the primary endpoint, 16 of 30 (53%) with a primary endpoint of OS and 20 of 53 (38%) with a primary endpoint of progression free survival (PFS) had an observed effect size less extreme than hypothesized; and 7 of 30 trials (23%) reported an observed effe...Continue Reading

References

Jun 18, 2002·The Oncologist·L Douglas CaseRobert Tucker
Jan 1, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher M Booth, Ian Tannock
Sep 17, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leonard B Saltz
Dec 7, 2010·Journal of the National Cancer Institute·Alberto Ocana, Ian F Tannock
Nov 14, 2013·Clinical Genitourinary Cancer·Bernard EscudierCamillo Porta
Mar 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adrian G SacherNatasha B Leighl
Mar 19, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lee M EllisLowell E Schnipper
Feb 2, 2015·The Lancet Oncology·Michelle K WilsonAmit M Oza
Jun 24, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lowell E Schnipper American Society of Clinical Oncology
Jun 2, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lowell E SchnipperRichard L Schilsky
Jun 7, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lowell E Schnipper, Richard L Schilsky
Jun 27, 2017·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·N GrössmannC Wild
Sep 26, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N I ChernyE G E de Vries

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Citations

Jul 3, 2021·Cancers·Julien PéronGilles Freyer
Jun 22, 2021·Journal of the National Comprehensive Cancer Network : JNCCN·Changyu ShenDhruv S Kazi

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