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

被引：86

作者：

Shi, Qian ^{[1
]}

de Gramont, Aimery ^{[2
]}

Grothey, Axel ^{[1
]}

Zalcberg, John ^{[5
]}

Chibaudel, Benoist ^{[2
]}

Schmoll, Hans-Joachim ^{[7
]}

Seymour, Matthew T. ^{[11
]}

Adams, Richard ^{[12
]}

Saltz, Leonard ^{[13
]}

Goldberg, Richard M. ^{[14
]}

Punt, Cornelis J. A. ^{[15
]}

Douillard, Jean-Yves ^{[4
]}

Hoff, Paulo M. ^{[16
]}

Hecht, Joel Randolph ^{[17
]}

Hurwitz, Herbert ^{[18
]}

Diaz-Rubio, Eduardo ^{[19
]}

Porschen, Rainer ^{[8
]}

Tebbutt, Niall C. ^{[6
]}

Fuchs, Charles ^{[20
]}

Souglakos, John ^{[21
]}

Falcone, Alfredo ^{[22
]}

Tournigand, Christophe ^{[3
]}

Kabbinavar, Fairooz F. ^{[17
]}

Heinemann, Volker ^{[9
]}

Van Cutsem, Eric ^{[23
]}

Bokemeyer, Carsten ^{[10
]}

Buyse, Marc ^{[24
]}

Sargent, Daniel J.

机构：

[1] Mayo Clin, Rochester, MN 55905 USA

[2] Hosp St Antoine, Paris, France

[3] Univ Paris Est Creteil, Paris, France

[4] Inst Canc Res Western, St Herblain, France

[5] Monash Univ, Melbourne, Vic 3004, Australia

[6] Austin Hlth, Melbourne, Vic, Australia

[7] Univ Halle Wittenberg, D-06108 Halle, Germany

[8] Klinikum Bremen Ost, Bremen, Germany

[9] Univ Munich, Munich, Germany

[10] Univ Hamburg Hosp, Hamburg, Germany

[11] Canc Res UK Clincal Ctr, Leeds, W Yorkshire, England

[12] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales

[13] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[14] Ohio State Univ, Columbus, OH 43210 USA

[15] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands

[16] Hosp Sirio Libanes, Sao Paulo, Brazil

[17] Univ Calif Los Angeles, Los Angeles, CA USA

[18] Duke Univ, Durham, NC USA

[19] Hosp Clin San Carlos, Madrid, Spain

[20] Dana Farber Canc Inst, Boston, MA 02115 USA

[21] Univ Crete, Iraklion, Greece

[22] Univ Pisa, Pisa, Italy

[23] Univ Hosp Gasthuisberg, Leuven, Belgium

[24] Int Inst Drug Dev, Louvain La Neuve, Belgium

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 01期

关键词：

PHASE-III TRIAL; COMBINATION CHEMOTHERAPY; INFUSIONAL FLUOROURACIL; PLUS OXALIPLATIN; CLINICAL-TRIALS; MUTATION STATUS; DOUBLE-BLIND; FINAL REPORT; LEUCOVORIN; CETUXIMAB;

D O I：

10.1200/JCO.2014.56.5887

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose 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. Methods 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. Results 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. Conclusion 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. (C) 2014 by American Society of Clinical Oncology

引用

页码：22 / U47

页数：13

共 43 条

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