Cardiac safety in patients (pts) with metastatic breast cancer (MBC) treated with lapatinib (L) and trastuzumab (TRA)

Abstract

514 Background: Clearly defined standards for assessing cardiac toxicity do not exist for newer agents used as treatment for BC, e.g., tyrosine kinase inhibitors. To evaluate the usefulness of increased cardiac monitoring and cardiac function (LVEF) in pts treated with L+TRA, data from 4 trials were analyzed. Methods: From July 2003 to Dec 2006, 238 pts received L+TRA (n=203) or L+TRA with paclitaxel or docetaxel (n=35) for HER2-positive MBC. LVEF was evaluated at screening, every 8 weeks after starting L+TRA, and at withdrawal via multiple-gated acquisition scans or echocardiograms. Rate of symptomatic cardiac events (CE; NCI CTCAE Grade 3 or 4 LV systolic dysfunction) or asymptomatic LVEF decreases (=20% relative to baseline and below the institution’s lower limit of normal) were assessed. Results: None of the 238 pts had a symptomatic CE. Four pts had a single asymptomatic LVEF decrease and 1 pt had 2 asymptomatic LVEF decreases, totaling 6 decreases in 5 (2.1%) pts. These pts were women aged 36–64 years and had previously received anthracyclines (A; n=2), A+TRA (n=2), or unknown therapy (n=1). Median time to onset of LVEF decrease was 83 days; all but 1 decrease occurred within 75 days after initiating L+TRA (range: 18–221 days). Baseline LVEFs of 62%, 60%, 62%, 74% and 58% decreased to 47%, 46%, 45%, 45%, and 45%, respectively. L+TRA was temporarily interrupted in 3 pts and continued in 2 pts despite LVEF decrease. Per investigators, LVEF decrease resolved with no further sequelae in 4 pts (59%, 56%, 60%, and 50%) and was ongoing in 1 pt. Conclusion: Initial data indicate L+TRA or L+TRA with taxanes does not constitute a serious incremental cardiac risk and may not require more stringent cardiac monitoring than is used for A or TRA alone. The combined effect of HER2 inhibition with L+TRA appears not to increase the risk of CE in this population. No significant financial relationships to disclose.