Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma

Authors

  • Susan Halabi PhD,

    Corresponding author
    1. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina
    2. Alliance Statistical and Data Center, Duke University, Durham, North Carolina
    • Corresponding author: Susan Halabi, PhD, Department of Biostatistics and Bioinformatics, Duke University Medical Center, 2424 Erwin Rd, Durham, NC 27705; Fax: (919) 681–7918; susan.halabi@duke.edu.

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  • Brian Rini MD,

    1. Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio
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  • Bernard Escudier MD,

    1. Department of Cancer Medicine, Institut Gustave-Roussy, Villejuif, France
    2. Department of Medical Oncology, Centre Léon Bérard, Lyon, France
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  • Walter M. Stadler MD,

    1. Department of Medicine, University of Chicago Medical Center, Chicago, Illinois
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  • Eric J. Small MD

    1. Department of Urology, University of California at San Francisco, San Francisco, California
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  • Presented in abstract format at the American Society of Clinical Oncology Genitourinary Symposium; March 5-7, 2010; San Francisco, CA; and the American Society of Clinical Oncology Annual Meeting; June 4-7, 2010; Chicago, IL.

  • We thank Roche for sharing the AVOREN dataset. In addition, the authors thank Drs. Peter Compton, George Kong, and Nicola Moore for answering questions regarding the AVOREN database.

  • See editorial on pages 7–10, this issue.

Abstract

BACKGROUND

The current study was conducted to investigate the dependence between progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to explore whether PFS can be used as an intermediate endpoint of OS in this patient population.

METHODS

A total of 1381 patients from 2 prospective phase 3 trials (Cancer and Leukemia Group B [CALGB] 90206 and AVOREN) of interferon-alpha with or without bevacizumab were analyzed. Both trials recruited previously untreated patients with clear cell mRCC with an Eastern Cooperative Oncology Group performance status of 0 to 2; adequate bone marrow, hepatic, cardiac, and renal function; and controlled blood pressure. The CALGB study served as the training data set, and the AVOREN study served as the testing data set. The dependence between PFS and OS was investigated using the Kendall tau for bivariate time-to-event endpoints.

RESULTS

In the training data set, the median OS times among patients who experienced progressive disease at 3 months or 6 months were 6 months and 8 months, respectively, compared with 25 months and 30 months, respectively, (P < .001) in patients who did not develop disease progress. The adjusted hazard ratios (HR) were 2.6 (P < .0001) and 2.8 (P < .0001), respectively, for patients who did and did not progress at 3 months or 6 months. The dependence between PFS and OS was 0.53. These associations were confirmed in the testing data set.

CONCLUSIONS

In patients with mRCC who were treated with interferon-alpha with or without bevacizumab, the PFS at 3 months and 6 months was found to be predictive of OS. A high dependence between PFS and OS was observed, suggesting that PFS may be used as a surrogate endpoint for OS. Although this is a novel observation for RCC, these findings require validation in patients with mRCC who are treated with other targeted agents. Cancer 2014;120:52–60. © 2013 American Cancer Society.

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