Impact of taxanes in association with anthracyclines in 1st line chemotherapy for metastatic breast cancer (MBC): Comprehensive review of 2805 patients in 7 phase III trials

Abstract

659 Background: The real advantage of taxanes in adjunction to antracycline-based chemotherapy in 1st line MBC is still unclear. We performed a comprehensive review (not a meta-analysis) (Simes, Stat Med 1987) including all phase III trials of 1st line chemotherapy for MBC, to look if the combination of antracyclines (doxo- or epi-rubicin) plus taxanes (paclitaxel or docetaxel) (AT) adds some benefit over standard antracicline-based regimen (AnonT) in activity and efficacy. Methods: We included phase III (prospective and randomized) published or presented at ASCO, ESMO/ECCO between 2000 and 2003; randomized phase II were excluded. Analysis was accomplished to look at significant differences in 1) time to progression (TTP); 2) overall response rate (ORR); 3) overall survival (OS) 4) complete response rate (CR) and 5) WHO G3–4 per patient toxicity (neutropenia, febrile neutropenia, FN, cardiotoxicity and neurotoxicity). For these analyses, ratios (HR and RR) and 95% confidence intervals (CI) were derived. Results: We gathered 7 trials (3 published and 4 presented) which account overall 2806 patients (pts). Pts characteristics were similar within each trial. When AT and AnonT were pooled and compared, significant differences were seen in ORR (HR 1,36, 95% CI 1,07–1,36; data on 2805 pts), CR (RR 2,04, 95% CI 1,13–3,68; data on 2100 pts), neutropenia (RR 1,19, 95% CI 1,09–1,31; data on 2805 pts), FN (RR 2,82, 95% CI 1,01–7,84; data on 2100 pts), neurotoxicity (RR 13,2, 95% CI 1,51–114,98; data on 1892 pts). A borderline significance in favor of AT were present in TTP (HR 1,10, 95% CI 1,00–1,21; data on 2805 pts). Not significant trend in favor of AT were seen in OS (HR 1,05, 95% CI 0,90–1,22; data on 2376 pts), and cardiotoxicity (RR 3,48, 95% CI 0,68–17,72; data on 1884 pts). Conclusions: The adjunction of taxanes to antracyclines in 1st line chemotherapy for MBC pts seems to add a significant benefit in activity (ORR, CR), and a slight advantage in TTP versus standard comparator arm. OS didn't seem significantly greater. Neutropenia, FN and neurotoxicity are significantly higher. No significant financial relationships to disclose.