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

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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.

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Abbreviations

ASCO:

American Society of Clinical Oncology

AUC:

Area under the curve

CI:

Confidence interval

HR:

Hazard ratio

OS:

Overall survival

PFS:

Progression-free survival

ROC:

Receiver-operating characteristic

TTP:

Time-to-progression

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Acknowledgments

The study was funded by Bayer Healthcare Pharmaceutical Inc.

Conflict of interest

Giovanna Devercelli and István Molnár are employees of Bayer Healthcare Pharmaceutical Inc. Costel Chirila, Dawn Odom, Shahnaz Khan, Bintu Sherif, James Kaye, and Beth Sherrill, are employees of RTI Health Solutions and received funding from Bayer Healthcare Pharmaceutical Inc. to perform the analyses reported in this manuscript.

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Authors and Affiliations

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

    Costel Chirila, Dawn Odom, Bintu N. Sherif & Beth Sherrill

  2. Global Health Economics and Outcomes Research, Bayer HealthCare Pharmaceuticals Inc, PO Box 1000, Montville, NJ, 07045, USA

    Giovanna Devercelli

  3. Market Access and Health Outcomes Strategy, RTI Health Solutions, 200 Park Offices Drive, Research Triangle Park, NC, 27709, USA

    Shahnaz Khan

  4. Epidemiology, RTI Health Solutions, 1440 Main Street, Suite 310, Waltham, MA, 02451-1623, USA

    James A. Kaye

  5. Global Clinical Development, Bayer HealthCare Pharmaceuticals Inc, PO Box 1000, Montville, NJ, 07045, USA

    István Molnár

Authors
  1. Costel Chirila
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  2. Dawn Odom
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  3. Giovanna Devercelli
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  4. Shahnaz Khan
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  5. Bintu N. Sherif
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  6. James A. Kaye
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  7. István Molnár
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  8. Beth Sherrill
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Corresponding author

Correspondence to Costel Chirila.

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Chirila, C., Odom, D., Devercelli, G. et al. Meta-analysis of the association between progression-free survival and overall survival in metastatic colorectal cancer. Int J Colorectal Dis 27, 623–634 (2012). https://doi.org/10.1007/s00384-011-1349-7

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  • DOI: https://doi.org/10.1007/s00384-011-1349-7

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