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Title: Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.
Austin Authors: Shi, Qian;de Gramont, Aimery;Grothey, Axel;Zalcberg, John;Chibaudel, Benoist;Schmoll, Hans-Joachim;Seymour, Matthew T;Adams, Richard A;Saltz, Leonard;Goldberg, Richard M;Punt, Cornelis J A;Douillard, Jean-Yves;Hoff, Paulo M;Hecht, Joel Randolph;Hurwitz, Herbert;Díaz-Rubio, Eduardo;Porschen, Rainer;Tebbutt, Niall C ;Fuchs, Charles;Souglakos, John;Falcone, Alfredo;Tournigand, Christophe;Kabbinavar, Fairooz F;Heinemann, Volker;Van Cutsem, Eric;Bokemeyer, Carsten;Buyse, Marc;Sargent, Daniel J
Affiliation: Charles Fuchs, Dana-Farber Cancer Institute, Boston, MA; John Souglakos, University of Crete, Heraklion, Greece
Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.
Matthew T. Seymour, Cancer Research UK Clincal Center, Leeds; Richard Adams, Cardiff University, Cardiff, United Kingdom; Leonard Saltz, Memorial Sloan-Kettering Cancer Center, New York, NY; Richard M. Goldberg, Ohio State University, Columbus, OH; Cornelis J.A. Punt, Academic Medical Center, Amsterdam, the Netherlands; Paulo M. Hoff, Hospital Sírio-Libanês, Sao Paulo, Brazil
Qian Shi, Axel Grothey, and Daniel J. Sargent, Mayo Clinic, Rochester, MN; Aimery de Gramont and Benoist Chibaudel, Hospital Saint Antoine; Christophe Tournigand, Université Paris Est Créteil, Paris; Jean-Yves Douillard, Institute of Cancer Research in Western, St Herblain, France
Hans-Joachim Schmoll, Martin-Luther University, Halle; Rainer Porschen, Klinikum Bremen-Ost, Bremen; Volker Heinemann, University of Munich, München; Carsten Bokemeyer, University Hospital, Hamburg-Eppendorf, Germany
Alfredo Falcone, University of Pisa, Pisa, Italy; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven; and Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium.
John Zalcberg, Monash University; Niall C. Tebbutt, Austin Health, Heidelberg, Victoria, Australia
Joel Randolph Hecht and Fairooz F. Kabbinavar, University of California at Los Angeles, Los Angeles, CA; Herbert Hurwitz, Duke University, Durham, NC; Eduardo Díaz-Rubio, Hospital Clinico San Carlos, Madrid, Spain
Issue Date: 10-Nov-2014
Publication information: Journal of Clinical Oncology 2014; 33(1): 22-8
Abstract: Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination.Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models.Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy.In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.
Gov't Doc #: 25385741
DOI: 10.1200/JCO.2014.56.5887
Journal: Journal of Clinical Oncology
Type: Journal Article
Subjects: Adult
Aged, 80 and over
Angiogenesis Inhibitors.therapeutic use
Antineoplastic Agents.therapeutic use
Biomedical Research.methods.statistics & numerical data
Colorectal Neoplasms.drug therapy.pathology
Databases, Factual.statistics & numerical data
Digestive System.drug effects.pathology
Disease-Free Survival
Middle Aged
Neoplasm Metastasis
Neoplasms.drug therapy.pathology
Outcome Assessment (Health Care).methods.statistics & numerical data
Protein Kinase Inhibitors.therapeutic use
Randomized Controlled Trials as Topic
Receptor, Epidermal Growth Factor.antagonists & inhibitors
Young Adult
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