Response to second-line chemotherapy (Ctx) in advanced urothelial carcinoma: A pooled retrospective analysis of the correlation between objective response rate (ORR) and progression-free survival (PFS) and overall survival (OS).

Abstract

354 Background: Second-line ctx for advanced urothelial carcinoma (UC) constitutes a substantial unmet need. A commonly used endpoint in phase II studies is ORR, however it is unclear whether this translates to a benefit in OS and PFS. We previously examined pooled OS, PFS, ORR and DCR in second line ctx in advance UC. We now are now determining whether increased ORR correlates with improved PFS and OS. Methods: Published second-line studies were identified from PubMed between 1997- 2012 and were reviewed for data extraction. Pearson correlation coefficient was used to determine correlation between ORR and OS and PFS. Results: 25 prospective studies of second-line ctx for progressive advanced UC were identified (22 non-randomised, 3 randomised) (n= 1,297). The majority of studies (88%) were phase II. 12 studies investigated combination regimens and 13 studies monotherapy. All studies allowed adjuvant and primary chemotherapy as first-line but only 7 studies reported median time from last chemotherapy. The range of reported response rates were 1% - 29%. ORR is moderately correlated to PFS (r= 0.42 {0.01 - 0.71} p = 0.04) and OS (r=0.67 {0.39 - 0.84} p = <0.01) in the entire cohort. When we compared the combination regimens to monotherapy the ORR was 27.7% versus 12.3% (p<0.01). The reported response rate for monotherapy was 8.6% - 27.7% and there was no correlation between ORR and PFS (r=0.26 {-0.37 - 0.72} p=0.42) and OS (r = 0.35 {-0.25 - 0.76} p=0.24). Conversely with combination regimens, response rates were 7% - 60% and ORR strongly correlated to PFS (r= 0.78 {0.40 - 0.93} p =<0.001) and OS (r=0.80 {0.43 - 0.94}, p=<0.001). Conclusions: The analysis revealed that ORR translated to a survival benefit. In second line ctx for advanced UC, responses to combination therapy only yielded a survival benefit. This may be appropriate approach in patients with a good performance status.