Anthracycline-rechallenge using pegylated liposomal doxorubicin (PLD) in previously treated patients with metastatic breast cancer (MBC): A meta-analysis using pooled individual data from four prospective trials

Abstract

1047 Background: Few data are available on the efficacy of anthracycline rechallenge using PLD. Methods: Pooled individual data from 4 prospective trials (Keller, J Clin Oncol. 2004; O'Brien, Ann Oncol. 2004; Al-Batran, Br J Cancer. 2006; and Al-Batran, Oncology. 2006) were utilized to evaluate the activity of PLD in pts with MBC previously treated with conventional anthracyclines. Primary endpoint was clinical benefit rate (CBR), defined as objective response or stable disease, both lasting ≥ 6 months. CBR was assessed in the entire group (primary hypothesis CBR ≥ 30%) and in pre-defined subgroups of pts depending on the most important features of their prior anthracycline-based therapy. Results: The studies comprised a total 935 pts, of whom 274 pts had received PLD after prior exposure to conventional anthracyclines. At the time of PLD therapy, these (274) pts were heavily pre-treated for MBC (median lines of previous chemotherapy 4, range 1 to 9, and 93.4% of pts received PLD after ≥ 2 previous chemotherapies for MBC). Prior anthracycline treatment was adjuvant, anti-metastatic, or both in 14%, 46%, or 40% of pts, respectively. The overall CBR from PLD was 32.2% (95% CI, 26.7%-37.8%), with no difference between pts who were considered anthracycline resistant (based on the study records) and those who were not (31.9% vs. 31.6%, respectively; p = 1). There was also no difference in CBR from PLD between pts who received prior anthracyclines adjuvant only (33.3%), anti-metastatic only (34.4%) or both (29.4%; p = 0.71). There was a trend towards a higher CBR in pts who received PLD at > 12 months vs ≤ 12 months since the end of their prior conventional anthracycline treatment (34.2% vs. 26.3%, respectively; p = 0.21). Higher CBR (up to 47%) and longer survival times were observed in pts without taxane pretreatment or with a low number of previous chemotherapies, most likely reflecting a less advanced disease in these pts. Conclusions: This meta-analysis demonstrates a clinical benefit from PLD in MBC pts previously treated with multiple chemotherapies, including anthracyclines. Interestingly, the CBR was independent of resistance to, setting of, or time since previous conventional anthracycline therapy. [Table: see text]