New aromatase inhibitors (Ais) as 1st-line endocrine therapy (ET) in metastatic breast cancer (MBC): A pooled analysis of 3238 women from 8 phase III trials

Abstract

602 Background: Some of the new non-steroidal AIs (anastrozole and letrozole) have been registred for the treatment of first line ET for MBC. We previously presented the results of a pooled analysis of AIs in 2nd line ET for MBC (Carlini P, ASCO 2004). In order to assess the benefit in TTP and ORR of all AIs when compared to tamoxifen, we performed a pooled analysis including all phase-III trials with new AIs (letrozole, anastrozole, fadrazole, formestane, exemestane) as 1st-line ET for MBC. Methods: Entry criteria: published/presented phase-III studies evaluating AIs as 1st-line ET in MBC. Randomized phase-II trials were ruled out. Time to progression (TTP) and overall response rate (ORR) were our end-points. Event-based relative risk ratio (RR) and 95% confidence intervals (CI) were derived. Combined effect estimation was computed with a fixed-effect model. An heterogeneity test was applied as well. Results: Eight trials were eligible (3238 pts). Significant benefit in favour of AIs versus tamoxifen were seen in TTP (RR 0.83, 95% CI 0.76–0.90, p<0.001), although significant heterogeneity (p<0.00001). When considering only trials with non-steroidal AIs (6 studies, 2458 pts), a significant benefit in favour of AIs versus tamoxifen were seen in TTP (RR 0.80, 95% CI 0.73–0.89, p<0.001), although significant heterogeneity (p<0.0001). Significant benefit in favour of AIs versus tamoxifen were seen in ORR (RR 1.18, 95% CI 1.06–1.31, p=0.002), although significant heterogeneity (p<0.011). When considering only trials with non-steroidal AIs (6 studies, 2458 pts), a significant benefit in favour of AIs versus tamoxifen were seen in ORR (RR 1.19, 95% CI 1.06–1.36, p=0.005), although significant heterogeneity (p=0.04). Conclusions: When all subgroups were analyzed for TTP and ORR, significant differences were found. AIs in 1st-line ET for MBC seem to add a significant benefit versus tamoxifen. The significant heterogeneity of all outcomes requires a careful evaluation of these results No significant financial relationships to disclose.