Impact of Geographic Region on Benefit of Anticancer Agents Evaluated in International Phase III Clinical Trials

Abstract

ABSTRACT Aim: International collaboration is important for contemporary phase III randomized controlled trials (RCTs). Such collaboration allows for enhanced patient accrual and more generalizable results. The impact of geographic region on the outcomes of new anticancer agents is unclear. Here we analyze the impact of geographic region on the efficacy of newly approved anticancer agents. We hypothesized that compared to developed countries; the magnitude of benefit will be lower in developing countries. Methods: RCTs evaluating agents for treatment of advanced solid tumors approved by the US Food and Drug Administration between January 2000 and June 2013 were identified. Eligible studies explicitly documented an international, multicenter design and reported outcomes of the primary endpoint based on geographic regions. Hazard ratios (HR) and 95% confidence intervals (CI) for overall (OS) or progression free survival (PFS) were extracted or estimated and pooled in a meta-analysis. The primary analysis was the comParison of developed vs. developing countries as defined by the World Bank, 2012. Secondary analyses included the comparison of Asian vs any non-Asian countries, Asian vs developed non-Asian countries, and Western Europe vs North America. Results: A total of 14 RCTs were eligible; 5 reported data for OS and 11 for PFS. Improvements in OS and PFS were significantly greater in developed compared to developing countries (see Table). No differences were observed in PFS between Asian and Non-Asian countries (subgroup difference P = 0.94); Asian and developed non-Asian countries (subgroup difference P = 0.09); or North America and Western Europe (Subgroup difference P = 0.57). Secondary analyses for OS were not possible due to lack of data. Outcome Pooled HR [95% CI] Developed Countries Pooled HR [95% CI] Developing Countries Subgroup difference P OS 0.73 [0.65-0.83] 0.94 [0.83-1.06] 0.005 PFS 0.54 [0.49-0.59] 0.69 [0.62-0.78] Conclusions: Patients from developed countries derive more benefit from new drugs than those from developing countries. This difference likely occurs due to differences in health systems or quality of supportive and palliative care or due to other undefined factors. Disclosure: All authors have declared no conflicts of interest.