The effect of different sequencing regimens of taxanes and anthracyclines in the primary systemic treatment (PST) of breast cancer (BC) patients (pts): M. D. Anderson Cancer Center retrospective analysis.

Abstract

548 Background: Taxane (T) and anthracycline (A) based regimens are commonly used sequentially in the PST setting in BC. It is unknown whether the efficacy of such combinations is affected by their sequence of administration. The purpose of this analysis was to assess the clinical relevance of different sequences of T and A in pts receiving PST. Methods: 1,414 pts with stage I-III BC were treated at MDACC between 1994-2009 with sequential PST T→A (84%) or A→T (16%). T-based and A-based regimens included only paclitaxel, and FAC/FEC regimens, respectively. Pts treated with trastuzumab or docetaxel were excluded. Results: The median follow up was 48.5 months and median age 50.2 years (range 23-83). 530 pts (37.4%) had stage I-IIA, 541 (38.2%) stage IIB-IIIA, and 343 (24.2%) stage IIIB-IIIC BC. 958 pts (67.7%) had hormone-receptor (HR) positive BC and 161 (11.3%), HER-2 positive. Because the two groups of patients were not identical in the distribution of prognostic factors at baseline, multivariate regression analysis (MVRA) were used to adjust for imbalances. pCR was observed in 12.4% and 20.9% patients treated with A→T and T→A respectively (OR 0.53, 95% CI 0.35-0.81; p = 0.003). In MVRA after adjustment for age, clinical stage, grade, LVI, HR and HER2 status, the sequence A→T was associated with a marginally significant lower likelihood of pCR (OR 0.63, CI 0.39-1.02; p = 0.059). In Cox univariate analysis A→T sequence was associated with higher risk of relapse (HR 1.95; CI 1.48-2.58 p < 0.0001) and death (HR 2.00; CI 1.46-2.75; p < 0.0001). In multivariate analysis, after stratification for period at diagnosis and adjustment for age, clinical stage, hormonal-receptor status, grade and LVI, AT sequence was associated with higher risk of relapse (HR 1.49 CI 1.10-2.03; p = 0.01) but not significantly associated with survival (HR 1.28; CI 0.90-1.84, p = 0.17). Conclusions: In this retrospective analysis, sequential T→A compared to A→T regimens in the PST setting was associated with higher likelihood of pCR and lower risk of relapse. These results are hypothesis-generating and should lead to prospective comparisions of the two sequences. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis Novartis