Cardiac safety of pegylated liposomal doxorubicin after conventional doxorubicin exposure in patients with sarcoma and breast cancer.

Abstract

388 Background: Lifetime cumulative doses of conventional doxorubicin (>450 mg/m2) are associated with dose-dependent cardiotoxicity. In soft tissue sarcoma (STS) and breast cancer, conventional doxorubicin is often utilized in earlier lines of therapy, whereas pegylated liposomal doxorubicin (PLD) is typically reserved for recurrent and metastatic disease. PLD is associated with less cardiotoxicity than conventional doxorubicin and high doses of PLD can be administered without increased risk of cardiotoxicity in patients without prior exposure to conventional doxorubicin. Limited data exists evaluating cardiotoxicity associated with PLD treatment after conventional doxorubicin, especially when doxorubicin lifetime doses approach the established cumulative total lifetime dose of 450-550 mg/m2. This study aims to evaluate the cardiac safety of PLD use in patients who had prior exposure to conventional doxorubicin. Methods: This was a single-center, observational, retrospective cohort study conducted in patients ≥18 years with STS or breast cancer, who were exposed to conventional doxorubicin from an earlier line of treatment prior to PLD between January 2010 – May 2022. Patients participating in clinical trials were excluded. The primary outcome of the study was cardiac safety. Cardiac toxicity was defined as ≥ 10% decrease in left ventricle ejection fraction (LVEF) or new diagnosis of heart failure within 6 months after PLD cessation. Results: 494 patients were screened and 50 patients met inclusion criteria, 8 STS and 42 breast cancer patients. Median lifetime cumulative conventional doxorubicin dose in patients with STS was 450 mg/m2 with a max dose of 825 mg/m2, and 240 mg/m2 with a max dose of 300 mg/m2 in breast cancer patients. Median lifetime cumulative PLD dose was 105 mg/m2 (range: 35-150 mg/m2) in the STS group and 105 mg/m2 (range: 35-510 mg/m2) in the breast cancer group. A decrease of ≥ 10% in LVEF was not observed in the STS group. 22 breast cancer patients had available LVEF data on PLD; 3 of these patients experienced ≥ 10% in LVEF drop and one of three patients was diagnosed heart failure. The average cumulative dose of PLD administered in patients with > 10% decrease in LVEF was 177 mg/m2 and had an average of 3.5 cycles. Most of STS patients initiated PLD treatment within 2 years after conventional doxorubicin while most breast patients initiated PLD treatment at least 10 years following conventional doxorubicin exposure. Conclusions: PLD administration in patients with prior exposure to conventional doxorubicin appears to be safe with limited cardiotoxicity in patients with STS and breast cancer. Future research is needed to determine if and how often routine cardiac monitoring is needed for patients on PLD without existing cardiac risk.