Liver Function Test (LFT) Elevations in Cancer Patients and Users of Tyrosine Kinase Inhibitor (TKI) Drugs

Liver Function Test (LFT) Elevations in Cancer Patients and Users of Tyrosine Kinase Inhibitor (TKI) Drugs Using the LabRx Database

A retrospective cohort study using the LabRx medical claims database will be performed to address these objectives. The primary objective of this project is to examine the background rates of liver function test (LFT) abnormalities in cancer patients treated with tyrosine kinase inhibitors (TKIs).

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Tyrosine kinase inhibitors

Detailed Description

Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

• Study Type: Observational
• Enrollment (Actual): 3800

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Retrospective cohort study using the LabRx medical claims EMR database. This database contains medical claims information including diagnoses, treatments, medications, and laboratory results for 23.3 million US residents. The study cohort included adult patients (age ≥18 years) with any cancer diagnosed between October 1, 2004-June 1, 2009 who were treated with 1 one or more of the TKI agents-erlotinib, gefitinib, dasatinib, imatinib, nilotinib, or lapatinib. The index date for this cohort was the date of first administration or prescription of the TKI agent on or following the date of the first cancer diagnosis.

Description

Inclusion Criteria:

• Adult (age ≥18 years) with at least two ICD-9 codes for a particular cancer (ICD-9 code 140-208.9) within a 6 month timeframe and at least one code for a TKI drug that occurs on or after the first cancer diagnosis code
• At least one month (30 days) of enrolment prior to index date and three months (91 days) of follow-up post index date; and
• Continuous enrolment in the LabRx database during follow-up.

Exclusion Criteria:

• Less than 18 years old
• Less than one month (30 days) of enrolment prior to index date or three months (91 days) of follow-up post index date; and
• Not continuously enrolled in the LabRx database during follow-up.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cancer patients; Adults (age ≥18 years) with at least two ICD-9 codes for a particular cancer within a 6 month timeframe and at least one code for a TKI drug that occurs on or after the first cancer diagnosis code	Drug: Tyrosine kinase inhibitors; Lapatinib, erlotinib, gefitinib, dasatinib, imatinib, nilotinib (analyzed as a class of drugs, not by individual drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With ALT (Alanine Transaminase) >=3x (Times) Upper Limit of Normal (ULN)	Prevalence of patients with an ALT elevation >=3x ULN among patients who had liver function testing during the baseline period (30 days prior to initiation of TKI drug).	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Incidence of ALT >=3x ULN	Number of patients with ALT >=3 times ULN among patients with a normal ALT measurement during the baseline period (30 days prior to initiation of TKI drug). Normal is defined as an ALT <1 times ULN at baseline.	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Number of Hy's Law Patients (ALT or AST >= 3x ULN and ALP <2x ULN and BIL >= 2x ULN)	Prevalence of patients with Hy's Law (ALT or AST >=3x ULN and ALP <2x ULN and BIL >=2x ULN, where AST = aspartate transaminase, ALP = alkaline phosphatase, BIL= bilirubin) among patients who had liver function testing during the baseline period (30 days prior to initiation of TKI drug).	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Incidence of Hy's Law (ALT or AST >=3x ULN and ALP <2x ULN and BIL >=2x ULN)	Number of patients with Hy's Law (ALT or AST >= 3x ULN and ALP <2x ULN and BIL >= 2x ULN) among patients with normal ALT, AST, ALP, and BIL measurements during the baseline period (30 days prior to initiation of TKI drug). Normal is defined as an ALT AST, ALP, and BIL <1 times ULN at baseline.	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum ALT Elevation Reached During Follow-up	Number of patients whose maximum ALT elevation fell within the indicated ULN range among patients with at least one incident ALT elevation during follow-up	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Median Time to the Maximum ALT Elevation During Follow-up	Median time (in months) between index date and the date of maximum ALT elevation.	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Maximum AST Elevation Reached During Follow-up	Number of patients whose maximum AST elevation fell within the indicated ULN range among patients with at least one incident AST elevation during follow-up	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Median Time to the Maximum AST Elevation During Follow-up	Median time (in months) between index date and date of maximum AST elevation	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Maximum ALP Elevation Reached During Follow-up	Number of patients whose maximum ALP elevation fell within the indicated ULN range among patients with at least one incident ALP elevation during follow-up	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Median Time to the Maximum ALP Elevation During Follow-up	Median time (in months) between index date and date of maximum ALP elevation	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Maximum BIL Elevation Reached During Follow-up	Number of patients whose maximum BIL elevations fell within the indicated ULN range among patients with at least one incident BIL elevation during follow-up	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Median Time to the Maximum BIL Elevation During Follow-up	Median time (in months) between index date and date of maximum BIL elevation	Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): October 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: April 1, 2010
• First Submitted That Met QC Criteria: April 1, 2010
• First Posted (ESTIMATE): April 2, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Tyrosine Kinase Inhibitor; Liver function
• Other Study ID Numbers: 113153; WEUKSTV3635 (OTHER: GSK); EPI40661 (OTHER: GSK)