Abstract
Progression-free survival and time-to-progression (PFS/TTP) are used commonly as primary
end-points in trials evaluating treatments for metastatic breast cancer (MBC). We
reviewed the impact of censoring on interpretation of these end-points. A systematic
review identified phase 3 trials in MBC published between 2001 and 2012 that reported
hazard ratios (HRs) for PFS/TTP and Kaplan–Meier curves indicating numbers at risk.
We calculated HRs for time-to-treatment-failure (TTF) where discontinuation of treatment
for any reason is considered an event. Mean HRs for PFS/TTP, TTF, and overall survival
(OS) were 0.79, 0.89 and 0.91, respectively. Unbalanced censoring of patients prior
to progression was prevalent, usually with more patients censored in the experimental
arms. There was moderate-to-poor correlation of HRs of PFS/TTP and TTF with HRs for
OS. We suggest that TTF should be reported as supportive analysis in registration
trials and extent of missing data due to censoring be considered in decisions made
by regulatory agencies.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Overview: progression-free survival as an endpoint in clinical trials with solid tumors.Clin Cancer Res. 2013; 19: 2607-2612
- Detecting an overall survival benefit that is derived from progression-free survival.J Natl Cancer Inst. 2009; 101: 1642-1649
- Progression-free survival: meaningful or simply measurable?.J Clin Oncol. 2012; 30: 1030-1033
- Surrogate endpoints in clinical trials: definition and operational criteria.Stat Med. 1989; 8: 431-440
- The clinical viewpoint: definitions, limitations of RECIST, practical considerations of measurement.Clin Cancer Res. 2013; 19: 2629-2636
- Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.Stat Med. 1998; 17: 2815-2834
- Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.N Engl J Med. 2012; 366: 520-529
- Everolimus plus exemestane for hormonereceptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2.Ann Oncol. 2014; 25: 2357-2362
- Missing data handling methods in medical device clinical trials.J Biopharm Stat. 2009; 19: 1085-1098
- Role of sensitivity analyses in assessing progression-free survival in late-stage oncology trials.J Clin Oncol. 2009; 27: 5958-5964
FDA May 2007. Guidance for Industry: Clinical Trail Endpoints the Approval of Cancer Drugs and Biologics. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071590.pdf [accessed October 07, 2014].
Article info
Publication history
Published online: February 26, 2015
Accepted:
December 22,
2014
Received in revised form:
October 16,
2014
Received:
June 12,
2014
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
