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Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

Authors Singh S, Wang X, Law C

Received 31 January 2014

Accepted for publication 1 May 2014

Published 16 August 2014 Volume 2014:4 Pages 103—113

DOI https://doi.org/10.2147/GICTT.S61671

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Simron Singh,1 Xufang Wang,2 Calvin HL Law1

1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA

Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression) and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022). In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713). The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed.

Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

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