Cancer
Conditions
Keywords
Liver function, Tyrosine Kinase Inhibitor
Brief summary
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).
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.
Interventions
Lapatinib, erlotinib, gefitinib, dasatinib, imatinib, nilotinib (analyzed as a class of drugs, not by individual drug)
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With ALT (Alanine Transaminase) >=3x (Times) Upper Limit of Normal (ULN) | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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). |
| Incidence of ALT >=3x ULN | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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. |
| Number of Hy's Law Patients (ALT or AST >= 3x ULN and ALP <2x ULN and BIL >= 2x ULN) | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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). |
| Incidence of Hy's Law (ALT or AST >=3x ULN and ALP <2x ULN and BIL >=2x ULN) | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum ALP Elevation Reached During Follow-up | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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 |
| Median Time to the Maximum 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 (in months) between index date and date of maximum ALP elevation |
| Maximum ALT Elevation Reached During Follow-up | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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 |
| Median Time to the Maximum 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 (in months) between index date and date of maximum BIL elevation |
| Maximum BIL Elevation Reached During Follow-up | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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 |
| Median Time to the Maximum 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 (in months) between index date and the date of maximum ALT elevation. |
| Maximum AST Elevation Reached During Follow-up | Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date. | 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 |
| Median Time to the Maximum 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 (in months) between index date and date of maximum AST elevation |
Participant flow
Pre-assignment details
This observational study was conducted and supported by GlaxoSmithKline.
Participants by arm
| Arm | Count |
|---|---|
| TKI Cohort Adult (age \>=18 years) members of the LabRx database (A United States healthcare claims database containing the aggregated health claims experience of the covered lives managed by United Healthcare) with at least two International Classification of Disease (ICD)-9 codes for any cancer within a six-month timeframe and at least one code for an Epidermal Growth Factor Receptor (EGFR) targeted small molecule tyrosine kinase inhibitor (TKI) drug (erlotinib, gefitinib, dasatinib, imatinib, nilotinib, and lapatinib). TKI initiation must have occurred within 30 days prior to or any time after the first cancer diagnosis. The index date was the date of the first TKI prescription, and patients were followed from 30 days prior to the index date through the last visit in the database (which may be due to death or change in health plan), or the study cut-off date of June 1, 2009, whichever came first. | 3,800 |
| Total | 3,800 |
Baseline characteristics
| Characteristic | TKI Cohort |
|---|---|
| Age, Continuous | 57 Years STANDARD_DEVIATION 12 |
| Sex/Gender, Customized Female | 2061 participants |
| Sex/Gender, Customized Male | 1737 participants |
| Sex/Gender, Customized Unknown | 2 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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.
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had normal ALT (\<1x ULN) during baseline (within 30 days prior to the initiation of TKI drug)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TKI Cohort | Incidence of ALT >=3x ULN | 18 participants |
95% CI: [3.3, 9]
Primary
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.
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had normal ALT, AST, ALP, and BIL (\<1x ULN) during baseline (within 30 days prior to the initiation of TKI drug).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TKI Cohort | Incidence of Hy's Law (ALT or AST >=3x ULN and ALP <2x ULN and BIL >=2x ULN) | 1 participants |
95% CI: [0, 2]
Primary
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).
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had liver function testing within 30 days prior to the initiation of TKI drug).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TKI Cohort | Number of Hy's Law Patients (ALT or AST >= 3x ULN and ALP <2x ULN and BIL >= 2x ULN) | 2 participants |
95% CI: [0.1, 1.4]
Primary
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).
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had liver function testing within 30 days prior to the initiation of TKI drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TKI Cohort | Number of Patients With ALT (Alanine Transaminase) >=3x (Times) Upper Limit of Normal (ULN) | 11 participants |
95% CI: [0.9, 3.5]
Secondary
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
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident ALP elevation during follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TKI Cohort | Maximum ALP Elevation Reached During Follow-up | ALP: >=1x ULN to <2x ULN | 61 participants |
| TKI Cohort | Maximum ALP Elevation Reached During Follow-up | ALP: >=2x ULN to <3x ULN | 7 participants |
| TKI Cohort | Maximum ALP Elevation Reached During Follow-up | ALP: >=3x ULN to <5x ULN | 4 participants |
| TKI Cohort | Maximum ALP Elevation Reached During Follow-up | ALP: >=5x ULN to <10x ULN | 3 participants |
| TKI Cohort | Maximum ALP Elevation Reached During Follow-up | ALP: >=10x ULN | 0 participants |
Secondary
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
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident ALT elevation during follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TKI Cohort | Maximum ALT Elevation Reached During Follow-up | ALT: >=1x ULN to <3x ULN | 82 participants |
| TKI Cohort | Maximum ALT Elevation Reached During Follow-up | ALT: >=3x ULN to <5x ULN | 8 participants |
| TKI Cohort | Maximum ALT Elevation Reached During Follow-up | ALT: >=5x ULN to <10x ULN | 10 participants |
| TKI Cohort | Maximum ALT Elevation Reached During Follow-up | ALT: >=10x ULN to <20x ULN | 0 participants |
| TKI Cohort | Maximum ALT Elevation Reached During Follow-up | ALT: >=20x ULN | 1 participants |
Secondary
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
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident AST elevation during follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TKI Cohort | Maximum AST Elevation Reached During Follow-up | AST: >=1x ULN to <3x ULN | 87 participants |
| TKI Cohort | Maximum AST Elevation Reached During Follow-up | AST: >=3x ULN to <5x ULN | 8 participants |
| TKI Cohort | Maximum AST Elevation Reached During Follow-up | AST: >=5x ULN to <10x ULN | 3 participants |
| TKI Cohort | Maximum AST Elevation Reached During Follow-up | AST: >=10x ULN to <20x ULN | 2 participants |
| TKI Cohort | Maximum AST Elevation Reached During Follow-up | AST: >=20x ULN | 1 participants |
Secondary
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
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident BIL elevation during follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TKI Cohort | Maximum BIL Elevation Reached During Follow-up | BIL: >=1x ULN to <1.5x ULN | 46 participants |
| TKI Cohort | Maximum BIL Elevation Reached During Follow-up | BIL: >=1.5x ULN to <2x ULN | 9 participants |
| TKI Cohort | Maximum BIL Elevation Reached During Follow-up | BIL: >=2x ULN to <5x ULN | 8 participants |
| TKI Cohort | Maximum BIL Elevation Reached During Follow-up | BIL: >=5x ULN to <10x ULN | 4 participants |
| TKI Cohort | Maximum BIL Elevation Reached During Follow-up | BIL: >=10x ULN | 3 participants |
Secondary
Median Time to the Maximum ALP Elevation During Follow-up
Median time (in months) between index date and date of maximum ALP elevation
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident ALP elevation during follow-up.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TKI Cohort | Median Time to the Maximum ALP Elevation During Follow-up | ALP: >=1x ULN to <2x ULN | 5 months |
| TKI Cohort | Median Time to the Maximum ALP Elevation During Follow-up | ALP: >=2x ULN to <3x ULN | 3 months |
| TKI Cohort | Median Time to the Maximum ALP Elevation During Follow-up | ALP: >=3x ULN to <5x ULN | 11 months |
| TKI Cohort | Median Time to the Maximum ALP Elevation During Follow-up | ALP: >=5x ULN to <10x ULN | 8 months |
| TKI Cohort | Median Time to the Maximum ALP Elevation During Follow-up | ALP: >=10x ULN | 0 months |
Secondary
Median Time to the Maximum ALT Elevation During Follow-up
Median time (in months) between index date and the date of maximum ALT elevation.
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident ALT elevation during follow-up.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TKI Cohort | Median Time to the Maximum ALT Elevation During Follow-up | ALT: >=1x ULN to <3x ULN | 4 months |
| TKI Cohort | Median Time to the Maximum ALT Elevation During Follow-up | ALT: >=3x ULN to <5x ULN | 8 months |
| TKI Cohort | Median Time to the Maximum ALT Elevation During Follow-up | ALT: >=5x ULN to <10x ULN | 3 months |
| TKI Cohort | Median Time to the Maximum ALT Elevation During Follow-up | ALT: >=10x ULN to <20x | 0 months |
| TKI Cohort | Median Time to the Maximum ALT Elevation During Follow-up | ALT: >=20x ULN | 7 months |
Secondary
Median Time to the Maximum AST Elevation During Follow-up
Median time (in months) between index date and date of maximum AST elevation
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident AST elevation during follow-up.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TKI Cohort | Median Time to the Maximum AST Elevation During Follow-up | AST: >=10x ULN to <20x ULN | 7 months |
| TKI Cohort | Median Time to the Maximum AST Elevation During Follow-up | AST: >=20x ULN | 7 months |
| TKI Cohort | Median Time to the Maximum AST Elevation During Follow-up | AST: >=1x ULN to <3x ULN | 4 months |
| TKI Cohort | Median Time to the Maximum AST Elevation During Follow-up | AST: >=3x ULN to <5x ULN | 5 months |
| TKI Cohort | Median Time to the Maximum AST Elevation During Follow-up | AST: >=5x ULN to <10x ULN | 3 months |
Secondary
Median Time to the Maximum BIL Elevation During Follow-up
Median time (in months) between index date and date of maximum BIL elevation
Time frame: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
Population: Members of the TKI cohort who had at least one incident BIL elevation during follow-up.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TKI Cohort | Median Time to the Maximum BIL Elevation During Follow-up | BIL: >=1x ULN to <1.5x ULN | 3 months |
| TKI Cohort | Median Time to the Maximum BIL Elevation During Follow-up | BIL: >=1.5x ULN to <2x ULN | 3 months |
| TKI Cohort | Median Time to the Maximum BIL Elevation During Follow-up | BIL: >=2x ULN to <5x ULN | 4 months |
| TKI Cohort | Median Time to the Maximum BIL Elevation During Follow-up | BIL: >=5x ULN to <10x ULN | 8 months |
| TKI Cohort | Median Time to the Maximum BIL Elevation During Follow-up | BIL: >=10x ULN | 6 months |