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

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

Acknowledgment

The authors thank Tara B Gibson and Jennifer M Kulak, of ApotheCom, Yardley, PA, USA, for writing and editorial assistance, and Haitao Gao for assistance with statistics.

Author contributions

SS developed the concept, assisted in analyzing the results from the clinician survey, wrote the manuscript, reviewed the drafts, and approved the final draft for submission. XW analyzed the results, wrote the manuscript, reviewed the drafts, and approved the final draft for submission. CL developed the concept, assisted in analyzing the results from the clinician survey, wrote the manuscript, reviewed the drafts, and approved the final draft for submission.

Disclosure

SS has received research grants from Novartis and consulting fees and honoraria from Novartis and Pfizer. XW is an employee of and a stockholder in Novartis Oncology. CL has received research grants from Novartis Oncology and consulting fees from Pfizer Oncology and Novartis Oncology, and serves on the speakers bureau for Novartis Oncology. Financial support for writing and editorial assistance was provided by Novartis Pharmaceuticals, Inc., in compliance with international guidelines on Good Publication Practice.