Pooled analysis of overall response rate and overall survival in Phase II clinical trials of breast cancer

Abstract

Metastatic breast cancer requires more investigation because of its high incidence. Efforts to improve clinical trials, simplification of assessments rather than complex evaluation, and validation of clinical trial endpoints are ongoing. In this paper, we analyzed 410 Phase II clinical trials’ endpoints [418 Overall Response Rate (ORR) and 254 Overall Survival (OS)] to assess the efficacy and impact of anticancer agents in advanced/metastatic breast cancer. We estimated the treatment effects for OS and ORR using appropriate statistical tests. We determined that there is a moderate positive correlation between ORR and OS (R = 0.36, p < 0.0001, 95% CI 0.25-0.46). Moreover, ORR predicted the OS with a 12% accuracy (R-sq= 0.12). Interestingly, there was statistically significant difference found in the mean ORR between 1- ,2- and 3-agent trials. Furthermore, no significant difference was reflected in the OS for 2-and-3-agent trials, indicating the need for further validation of the surrogacy of ORR. Nonetheless, ORR is somewhat reliable surrogate of OS in phase II trials of breast cancer and we recommend finding a better surrogate than ORR.