Progress and trends in successful phase II clinical trials in advanced solid cancers over the past 20 years

Abstract

6556 Background: To identify progress and trends in phase II studies of advanced solid tumors over the past 20 years. Methods: From 1985 to 2005, all successful phase II clinical trials that resulted in a published phase III study were identified in PubMed, Cochrane Central Register of Controlled Trials, and BIOSIS. Over three study periods, 1985–1991, 1992–1998, and 1999–2006, data were analyzed using the chi square test and logistic regression models. Results: Of the 666 phase II studies that led to phase III trials, 186, 263, and 207 trials were identified in 1985–1991, 1992–1998, and 1999–2006, respectively. Compared to cancers such as breast and colon, the percentage of phase II trials on lung cancer increased from 12.2% to 23.2% to 31.9% over the three study periods (p 25–50) increased from 35.4% to 42.4% to 44.4%, respectively (p<0.001). There was also a significant increase in the percentage of trials performed at multiple rather than single-institutions (27.5% to 39.0% to 64.9%; p<0.001). The percentage of trials involving pharmaceutical groups increased across these time periods from 0.6% to 2.3% to 12.4% (p<0.001), while the percentage of trials from academic institutions decreased from 60.0% to 50.2% to 47.0% (p<0.001). There was a trend towards an increase in the proportion of positive compared to negative or equivocal outcomes for phase II clinical trials (p=0.005). The proportion of phase II studies that resulted in “positive” phase III trials increased from 24.5% to 34.2% to 50.6% (p<0.001). The percentage of phase II studies performed in the U.S. decreased from 51.7% to 44.9% to 34.0% (p<0.001), and an increase in European-based trials, from 38.5% to 50.0% to 51.7% (p<0.001). However, other factors such as median duration of response and survival were not significant over time. Conclusions: Over time, there was an increase in the proportion of lung cancer trials and a higher number of patients enrolled per clinical trial. In addition, more clinical trials were conducted in multiple rather than single institutions, in Europe instead of the U.S., and by pharmaceutical groups rather than academic centers. Identifying the progress and trends of successful phase II clinical trials may have significant implications toward the design and outcomes of future clinical trials. No significant financial relationships to disclose.