awaited analysis: cardiac safety of lapatinib

[Lani]

Lapatinib appears safe in patients with breast cancer
[American Society of Clinical Oncology]
NEW YORK (Reuters Health) - Pooled data from 44 studies indicate that the tyrosine kinase EGFR and HER2 inhibitor lapatinib exhibits low cardiotoxicity in cancer patients.
"This study," lead investigator Dr. Edith A. Perez told Reuters Health, "represents a thorough analysis of the prospectively collected data of more than 3,500 patients treated with lapatinib for HER2-positive breast cancer."
In the June issue of Mayo Clinic Proceedings, Dr. Perez of the Mayo Clinic in Jacksonville, Florida, and colleagues observe that HER2 pathway inhibitors can cause cardiac dysfunction.
However, cardiac events (i.e., decreases in left ventricular ejection fraction) were reported in only 60 (1.6%) of 3689 patients. Two patients had two such events. Fifty-three of the events were asymptomatic and these patients received no cardiac-related therapy.
In the 40 patients in whom cardiac outcome was determined, 35 (88%) had full or partial recovery, regardless of whether they continued or discontinued lapatinib. No cardiac deaths were attributed to lapatinib.
"The data," concluded Dr. Perez, "demonstrate a reassuringly low rate of clinically evident or asymptomatic cardiac effects. Further studies in comparative trials will allow us to place the data in the context of other anti-HER2 agents."


ABSTRACT: Cardiac Safety of Lapatinib: Pooled Analysis of 3689 Patients Enrolled in Clinical Trials
[Mayo Clinic Proceedings]
Objective: To analyze the cardiac safety of lapatinib, an oral, reversible, tyrosine kinase EGFR (ERBB1) and HER2 inhibitor, using prospective data collected in 44 clinical studies.
Patients and methods: Lapatinib (as monotherapy or in combination) was administered to 3689 patients in studies conducted between January 5, 2001, and September 30, 2006. Left ventricular ejection fraction (LVEF) was prospectively evaluated via multiple-gated acquisition scan or echocardiography at screening, every 8 weeks during therapy, and at withdrawal. We analyzed cardiac events defined as symptomatic (grade 3 or 4 left ventricular systolic dysfunction according to the National Cancer Institute Common Terminology Criteria for Adverse Events) or asymptomatic (LVEF decreases ≥20% relative to baseline and below the institution's lower limit of normal; no symptoms).
Results: A study-defined cardiac event was reported in 60 patients (1.6%) previously treated with anthracyclines (n=12), trastuzumab (n=14), or neither (n=34). These prior treatments were associated with a 2.2%, 1.7%, and 1.5% incidence of cardiac events, respectively. In most patients (53 patients, 83%), events were not preceded by symptoms. Mean times to onset and duration of LVEF decrease were 13.0 and 7.3 weeks, respectively. The decrease in LVEF was rarely severe; the mean nadir was 43%. In 40 patients for whom outcome was determined, 35 (88%) had a partial or full recovery regardless of continuation or discontinuation of lapatinib. No cardiac deaths occurred among patients treated with lapatinib.
Conclusion: Our review of data from 44 clinical studies revealed low levels of cardiotoxicity for lapatinib. Cardiac events were usually asymptomatic, caused reversible decreases in LVEF, and occurred at similar rates in patients who were and were not pretreated with anthracyclines or trastuzumab.

[hutchibk]

This is good news...

[Cathya]

Lani;

Does this include patients who have had AC and Taxol chemo or just lapatinib alone?

Thanks,

Cathy