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Int J Colorectal Dis. 2012 May;27(5):623-34. doi: 10.1007/s00384-011-1349-7. Epub 2011 Nov 12.

Meta-analysis of the association between progression-free survival and overall survival in metastatic colorectal cancer.

Author information

1
Biometrics, RTI Health Solutions, 200 Park Offices Drive, PO Box 12194, Research Triangle Park, NC 27709, USA. cchirila@rti.org

Abstract

PURPOSE:

The validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment.

METHODS:

We conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the "control" versus "experimental" arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis.

RESULTS:

We analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82-0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83-0.93)]. R(2) was 0.48 for PFS_TTP and 0.59 for PFS; R (2) for PFS_TTP was higher for first-line (R(2) = 0.54) than second-line studies (R(2) = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds.

CONCLUSIONS:

The correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data.

PMID:
22076612
DOI:
10.1007/s00384-011-1349-7
[Indexed for MEDLINE]

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