Concordance of study objectives with efficacy findings in metastatic breast cancer (MBC) treatment trials
6600 Background: Despite ongoing development of new agents, overall survival in MBC remains discouraging. We reviewed large randomized controlled trials (RCTs) published since 2000 to compare stated objectives with efficacy endpoints. Methods: Systematic review of RCTs of systemic antineoplastic treatment in advanced / metastatic breast cancer, published 2000–2006 in English. Studies enrolling fewer than 100 patients or performed only at sites outside North America and Europe were excluded. Study success was characterized with regard to the primary endpoint as described in prospective power calculations. Results: 68 RCTs, enrolling 24,956 patients, met inclusion criteria. The 68 RCTs comprised 83 efficacy comparisons due to multiple arms and/or more than one primary endpoint. Frequency of success was similar by geographic location and presence of industry sponsorship, but higher for noninferiority comparisons ( Table 1 ). 5 of 13 non-inferiority studies reported unplanned superiority findings for the experimental arm, while 11 of 39 studies failing to meet planned superiority endpoints made statements regarding equivalence or superiority to control treatments. For 10 of 20 successful superiority studies, reported results did not match/exceed planned between-group differences, though the comparisons reached statistical significance: 4 such studies substantially exceeded planned enrollment (2 of which recalculated sample size after reviewing interim data), while reasons for attaining superiority in 6 cases were unclear. Of the remaining 10 superiority comparisons, 4 reached significance due to underperforming control arms (enabling PFS/TTP differences of <2 months to establish superiority), 2 exceeded point estimates, and 4 exceeded estimated between- group ratios. Conclusions: Slippage from prospective study goals, even in large randomized trials, may contribute to a disconnect between the profusion of research activity and disappointing efficacy gains in MBC. No significant financial relationships to disclose. [Table: see text]