Relationship between 6- and 9-month progression-free survival and overall survival in patients with metastatic urothelial cancer treated with first-line cisplatin-based chemotherapy
Article first published online: 29 MAY 2013
Copyright © 2013 American Cancer Society
Volume 119, Issue 16, pages 3020–3026, 15 August 2013
How to Cite
Galsky, M. D., Krege, S., Lin, C.-C., Hahn, N., Ecke, T., Moshier, E., Sonpavde, G., Godbold, J., Oh, W. K. and Bamias, A. (2013), Relationship between 6- and 9-month progression-free survival and overall survival in patients with metastatic urothelial cancer treated with first-line cisplatin-based chemotherapy. Cancer, 119: 3020–3026. doi: 10.1002/cncr.28145
- Issue published online: 2 AUG 2013
- Article first published online: 29 MAY 2013
- Manuscript Accepted: 28 FEB 2013
- Manuscript Revised: 17 JAN 2013
- Manuscript Received: 10 DEC 2012
- urothelial cancer;
- bladder cancer;
- clinical trials;
- progression-free survival;
- overall survival;
Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with metastatic urothelial carcinoma (UC) is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS).
Data was pooled from 7 phase 2 and 3 trials evaluating cisplatin-based chemotherapy in metastatic UC. An independent cohort of patients enrolled on a phase 3 trial was used for external validation. Landmark analyses for progression at 6 and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.
A total of 364 patients were included in the initial cohort. The median PFS was 8.21 months (95% confidence interval = 7.43, 8.39) and the median OS was 13.50 months (95% confidence interval = 11.80, 15.67). In the landmark analysis, the median OS for patients who progressed at 6 months was 3.87 months compared with 15.06 months for those patients who did not progress (P < .0001) and the median OS for patients who progressed at 9 months was 5.65 months compared with 21.39 months for those patients who did not progress (P < .0001). A Fleischer model demonstrated a statistically significant dependent correlation between PFS and OS. The findings were externally validated in an independent cohort.
PFS at 6 and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy and could potentially serve as endpoints in (randomized) phase 2 trials to screen the activity of novel regimens. Cancer 2013;119:3020—3026. © 2013 American Cancer Society.