Complete Longitudinal Analyses of the Randomized, Placebo-Controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor following Imatinib Failure
George D Demetri, Christopher R Garrett, Patrick Schoffski, Manisha H Shah, Jaap Verweij, Serge Leyvraz, Herbert I Hurwitz, Antonio Lopez Pousa, Axel Le Cesne, David Goldstein, Luis Paz-Ares, Jean-Yves Blay, Grant A McArthur, Qiang Casey Xu, Xin Huang, Charles S Harmon, Vanessa Tassell, Darrel P Cohen, Paolo G Casali
CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2012
PURPOSE: To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes. EXPERIMENTAL DESIGN: Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore cross-over impact. Circulating levels of angiogenesis biomarkers were analyzed. RESULTS: In..View full abstract
Awarded by Spanish National Health Service
Awarded by NATIONAL CANCER INSTITUTE
G.D. Demetri has received commercial research support from Pfizer, Novartis, Ariad, Johnson & Johnson, Bristol-Myers Squibb, Infinity, and Daiichi-Sankyo, and has served as a consultant for Pfizer, Novartis, Ariad, Johnson & Johnson, Genentech, Infinity, Bayer, EMD-Serono, GlaxoSmithKline, Amgen, Daiichi-Sankyo, ArQule, Enzon, and Millenium/Takeda. He has also served as a member of an advisory board for ZioPharm. C.R. Garrett, L. Paz-Arez, and J. Verweij have served as consultants or members of advisory boards for Pfizer. P. Schoffski has received a commercial research grant, other commercial research support, and honoraria from speakers bureau from and has served as a consultant or member of an advisory board for Pfizer. M.H. Shah has received a commercial research grant from Pfizer. H.I. Hurwitz has received a commercial research grant and has served as a consultant or member of an advisory board for Pfizer. A. Le Cesne has received honoraria from speakers bureau from Pfizer, Novartis, and Pharmamar. D. Goldstein has received commercial research grants from Pfizer, Cellgene, and Amgen, and has received honoraria from and served as a member of advisory boards for Pfizer, Novartis, Bayer, GlaxoSmithKline, and Roche. J.-Y. Blay has received honoraria from speakers bureau from and has served as a consultant or member of advisory boards for Pfizer and Novartis. G.A. McArthur has received commercial research grants from Pfizer and Novartis. Q. Xu has served as a consultant for Pfizer. C.S. Harmon is a previous employee of and has had an ownership interest in Pfizer. X. Huang, V. Tassell, and D.P. Cohen are employees of and have ownership interests in Pfizer. P.G. Casali has received honoraria for lectures and/or for serving in an advisory role for Pfizer, Novartis, and Bayer.The authors thank all the participating patients and their families, as well as the global network of investigators (listed in Supplementary Data), research nurses, study coordinators, and operations staff. C.S. Harmon was an employee of Atrium Staffing (New York, NY) and was a paid contractor of Pfizer in the development of this article and the analysis and interpretation of data involving circulating biomarkers of angiogenesis. Medical writing support was provided by Wendy Sacks at ACUMED (New York, NY) and was funded by Pfizer Inc.This study was sponsored by Pfizer Inc. (New York, NY). Additional funding was provided by the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Rubenstein Foundation, the Katz Foundation, the Quick Family Fund for Cancer Research, the Ronald O. Perelman Fund for Cancer Research at Dana-Farber, the Stutman GIST Cancer Research Fund, Paul's Posse, and Leslie's Links (G.D. Demetri); and grant no. FIS PI 081156 from the Spanish National Health Service (L. Paz-Ares).