Cardiac safety of trabectedin monotherapy and in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer.

Abstract

11547 Background: Trabectedin (T) is an established option as monotherapy for advanced soft tissue sarcomas (STS; Leiomyosarcomas and Liposarcomas in the USA) and in combination with pegylated liposomal doxorubicin (PLD) for recurrent ovarian cancer (ROC). This retrospective analysis evaluated the cardiac safety profile in over 1500 patients (pts) from clinical trials administering T monotherapy for STS or in combination with PLD (T+PLD) for ROC. Methods: Integrated cardiac safety data was analyzed from ten Phase 2 trials and one Phase 3 trial in STS (T) and two Phase 3 ROC trials (T+PLD). Cardiac-related treatment-emergent adverse events (TEAEs) were summarized using MedDRA terminology and by Kaplan-Meier analysis for time-to-event variables. Subgroup analyses were performed for cardiac-related TEAEs, including any significant decrease in LVEF. Results: Integrated data on T monotherapy included 982 pts (Table). Of these, 110 (11.2%) pts who received ≥1 dose of T experienced a cardiac-related TEAE, including tachycardia (3.1%), palpitations (1.5%), LVEF decrease (1.3%), sinus tachycardia (1.0%), and/or congestive cardiac failure (1.0%). A multivariate analysis revealed factors associated with increased risk to be cardiovascular medical history (risk ratio [RR]: 1.90; 95% CI: 1.24-2.91; p = 0.003) and age > 65 years (RR: 1.78; 95% CI: 1.12,2.83; p = 0.014). Cardiac-related TEAEs were reported in 78 (12.6%) of 619 pts receiving T+PLD (Table). Incidence of cardiac-related TEAEs was greater with T+PLD compared with PLD monotherapy (12.6% vs 5.6%). A multivariate analysis showed that pts were at increased risk for experiencing cardiac-related TEAEs when treated with T+PLD compared to PLD monotherapy (RR: 2.70; 95% CI: 1.75,4.17; p < 0.0001) and when there was a history of prior cardiac medication (RR: 1.88; 95% CI: 1.16,3.05; p = 0.010). Conclusions: Although infrequent, patients receiving T after prior anthracyclines or in combination with PLD are at risk for cardiac dysfunction, and appropriate clinical awareness and monitoring is encouraged to optimize patient outcomes. [Table: see text]