Physician Liver Function Test (LFT) Monitoring for Tykerb Pts
Status:
Completed
Trial end date:
2011-08-01
Target enrollment:
Participant gender:
Summary
In July 2008, the lapatinib (Tykerb) Prescribing Information (label) was updated to include a
boxed warning related to hepatotoxcity and detailed instructions for monitoring liver
function before and during lapatanib exposure. For patient safety, it is of interest to know
the extent to which providers are adherent with these guidelines for hepatic monitoring of
lapatanib users.
Thus, the aim of this study is to determine if physicians conduct liver function testing
prior to prescribing lapatanib and at regular intervals during exposure, and if they withdraw
lapatanib, and do not re-treat, for patients who demonstrate severe liver enzyme elevations
while exposed. These aims will be tested in the "Pre-label" (prior to the boxed warning) and
"Post-label" (after the boxed warning) periods to determine if physician adherence to the
guidelines changed as a result of the warning.
Specifically, the boxed warning provided the following guidance:
"Hepatotoxicity (alanine transaminase or aspartate transaminase >3 times the upper limit of
normal and total bilirubin >1.5 times the upper limit of normal) has been observed in
clinical trials (<1% of patients) and postmarketing experience. The hepatotoxicity may be
severe and deaths have been reported. Causality of the deaths is uncertain. The
hepatotoxicity may occur days to several months after initiation of treatment. Liver function
tests (transaminases, bilirubin, and alkaline phosphatase) should be monitored before
initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated. If
changes in liver function are severe, therapy with lapatanib should be discontinued and
patients should not be re-treated with lapatanib"
The following objectives will be assessed and compared among patients prescribed lapatanib
before and after the addition of detailed guidance on liver function testing to the product
label on July 9, 2008:
1. Objective 1: Determine if physicians perform liver funtion tests (LFTs) prior to
prescribing lapatanib (baseline)
2. Objective 2: Describe the prevalence of LFT elevations at baseline
3. Objective 3: Determine if physicians routinely perform LFTs during the duration of
lapatanib exposure
4. Objective 4: Describe the cumulative incidence and incidence rate of LFT elevations
during lapatanib exposure
5. Objective 5: Describe patients that experience severe LFT elevations during lapatanib
exposure and calculate the proportion that have lapatanib discontinued and are not
re-treated
To achieve these objectives, an observational retrospective cohort study will be conducted
using the United States Oncology Electronic Medical Records database. The study population
will consist of females with a diagnosis of metastatic breast cancer and a documented order
for Lapatanib from January 1, 2007 - December 31, 2009. Patients will be categorized by
whether they initiated Lapatanib before or after the July 9, 2008 label change.
'Pre Label': Initiated lapatanib between January 1, 2007 and December 31, 2007. Follow-up
time for this group will continue until June 30, 2008 to allow these patients to have at
least six months of follow-up time prior to the label change.
'Post Label': Initiated lapatanib between July 9, 2008 and December 31, 2009. Follow-up time
for this group will continue until June 30, 2010 to allow these patients to have at least six
month of follow-up.
The exposure in this study is lapatanib oral medication. The date of initiation of lapatanib
will be the index date. Lapatanib exposure period(s) will be defined from the index date
through to the end of the study period (June 30, 2008 for pre-label group or June 30, 2010
for post-label group).
The project will use proportions and two estimates of incidence (cumulative incidence and
incidence rates using person-time) to describe the outcomes of interest among the users of
Lapatanib before and after the label change. The following LFTs will be considered:
- alanine transaminase (ALT)
- aspartate transaminase (AST)
- alkaline phosphatise (ALP)