Activity endpoints reported in soft tissue sarcoma phase II trials: quality of reported endpoints and correlation with overall survival

Background: Despite extensive research over the past 3 decades, few investigational drugs are considered as promising and these drugs failed to improve overall survival. Therefore we performed a systematic review of the literature to improve our understanding of the reasons that explain these failures.

Methods: We reviewed 53 phase II trial reports that investigated new treatments in patients with advanced soft tissue sarcoma from 1999 to 2011. We critically reviewed the selected primary endpoint used in these trials.

Results: Forty percent of trials were not interpretable because of major inherent methodological flaws. Only 3 primary endpoints were correlated with median overall survival (mOS): 3- and 6-month progression free rates and median progression-free survival. Nevertheless, the mOS was not significantly higher in the cases of active drugs.

Discussion: We need to improve the definition of primary active endpoints and develop better designs for future trials. The current definition of promising drugs must be refined.