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Tumor response and progression-free survival as potential surrogate endpoints for overall survival in extensive stage small-cell lung cancer.
- Source :
-
Cancer (0008543X) . 3/15/2011, Vol. 117 Issue 6, p1262-1271. 10p. 3 Charts, 3 Graphs. - Publication Year :
- 2011
-
Abstract
- BACKGROUND: The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS. METHODS: Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R² from weighted least squares regression model, Spearman correlation coefficient, and R² from bivariate survival model (Copula R2). RESULTS: Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.5, concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.4, 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R² = 0.79; Copula R² = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R² ≥ 0.48). CONCLUSIONS: PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0008543X
- Volume :
- 117
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cancer (0008543X)
- Publication Type :
- Academic Journal
- Accession number :
- 59129050
- Full Text :
- https://doi.org/10.1002/cncr.25526