| Abstract | PURPOSE: Our aims were to determine the correlations between progression-free survival (PFS), time to progression (TTP), and response rate (RR) with overall survival (OS) in the first-line treatment of metastatic colorectal cancer (MCRC), and to identify a potential surrogate for OS. METHODS: Randomized trials of first-line chemotherapy in MCRC were identified, and statistical analyses were undertaken to evaluate the correlations between the end points. RESULTS: Thirty-nine randomized controlled trials were identified containing a total of 87 treatment arms. Among trials, the nonparametric Spearman rank correlation coefficient (r(s)) between differences (Delta) in surrogate end points (DeltaPFS, DeltaTTP, and DeltaRR) and DeltaOS were 0.74 (95% CI, 0.47 to 0.88), 0.52 (95% CI, 0.004 to 0.81), 0.39 (95% CI, 0.08 to 0.63), respectively. The r(s) for DeltaPFS was not significantly different from the r(s) DeltaTTP (P = .28). Linear regression analysis was performed using hazard ratios for PFS and OS. There was a strong relationship between hazard ratios for PFS and OS; the slope of the regression line was 0.54 +/- 0.10, indicating that a novel therapy producing a 10% risk reduction for PFS will yield an estimated 5.4% +/- 1% risk reduction for OS. CONCLUSION: In first-line chemotherapy trials for MCRC, improvements in PFS are strongly associated with improvements in OS. In this patient population, PFS may be an appropriate surrogate for OS. As a clinical end point, PFS offers increased statistical power at a given time of analysis and a significant lead time advantage compared with OS. |
| Authors | Patricia A Tang, Søren M Bentzen, Eric X Chen, Lillian L Siu
(Affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.)
|
| Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 25
Issue 29
Pg. 4562-8
(Oct 10 2007)
ISSN: 1527-7755 United States |
| PMID | 17876010
(Publication Type: Journal Article, Review)
|
| Chemical References |
- Antineoplastic Agents
- Biological Markers
|
| Topics |
- Antineoplastic Agents
(therapeutic use)
- Biological Markers
- Clinical Trials as Topic
(economics, methods)
- Colorectal Neoplasms
(drug therapy, mortality)
- Disease Progression
- Disease-Free Survival
- Endpoint Determination
- Humans
- Neoplasm Metastasis
- Randomized Controlled Trials as Topic
(economics, methods)
- Regression Analysis
- Research Design
- Treatment Outcome
|
