• Costel Chirila, Dawn Odom, Giovanna Devercelli, Shahnaz Khan, Bintu N Sherif, James A Kaye, István Molnár, and Beth Sherrill.
• Biometrics, RTI Health Solutions, 200 Park Offices Drive, PO Box 12194, Research Triangle Park, NC 27709, USA. cchirila@rti.org
• Int J Colorectal Dis. 2012 May 1; 27 (5): 623-34.

PurposeThe 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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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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