Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: Meta-analysis

Background: Aromatase inhibitors and inactivators have been extensively tested in patients with advanced breast cancer, but it is unclear whether they offer any survival benefits compared with standard hormonal treatment with tamoxifen or progestagens. We performed a meta-analysis of randomized controlled trials that compared several generations of aromatase inhibitors and inactivators with standard hormonal treatment in patients with advanced breast cancer. Methods: The endpoint that we assessed was survival. Trials were located through searches of PubMed and Cochrane Library (last update March 2006). Relative hazards (RHs) were summarized across trials through fixed- and random-effects analyses, and heterogeneity was assessed with the Q and 12 statistics. All statistical tests were two-sided. Results: Twenty-five different comparisons, with a total of 8504 patients, were included in the meta-analysis. We found statistically significant survival benefits with third-generation aromatase inhibitors and inactivators (vorozole, letrozole, examestane, and anastrazole) (RH = 0.87, 95% confidence interval [CI] = 0.82 to 0.93; P < .001) but not with first-generation (aminoglutethimide) or second-generation (formestane and fadrozole) agents. The difference in the summary effects between these two groups of trials was statistically significant (P = .04). The survival benefit with third-generation agents in first-line trials, in which these agents were compared with tamoxifen (11% RH reduction, 95% CI = 1% to 19%; P = .03), was identical to their benefit in second- and subsequent-line trials in which these agents were compared with other treatments (14% RH reduction, 95% Cl = 6% to 21%; P < .001). Conclusions: Inhibition of the aromatase system, in particular with third-generation aromatase inhibitors and inactivators, appears to be associated with statistically significant improved survival of patients with advanced breast cancer compared with standard hormonal treatments.