Trial Outcomes & Findings for Liver Function Test (LFT) Elevations in Cancer Patients and Users of Tyrosine Kinase Inhibitor (TKI) Drugs (NCT NCT01098500)

NCT ID: NCT01098500

Last Updated: 2017-05-30

Results Overview

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).

• Recruitment status: COMPLETED
• Target enrollment: 3800 participants
• Primary outcome timeframe: Study period was October 1, 2004-June 30, 2009. Patients had at least 91 days of follow-up post index date.
• Results posted on: 2017-05-30

Participant Flow

This observational study was conducted and supported by GlaxoSmithKline.

Participant milestones

Measure	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.
Overall Study STARTED	3800
Overall Study COMPLETED	3800
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	TKI Cohort n=3800 Participants 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.
Age, Continuous	57 Years STANDARD_DEVIATION 12 • n=5 Participants
Sex/Gender, Customized Female	2061 participants n=5 Participants
Sex/Gender, Customized Male	1737 participants n=5 Participants
Sex/Gender, Customized Unknown	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure

TKI Cohort n=498 Participants 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.

Number of Patients With ALT (Alanine Transaminase) >=3x (Times) Upper Limit of Normal (ULN)

11 participants

PRIMARY outcome

Timeframe: 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)

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.

Outcome measures

Measure

TKI Cohort n=344 Participants 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.

Incidence of ALT >=3x ULN

18 participants

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Measure

TKI Cohort n=500 Participants 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.

Number of Hy's Law Patients (ALT or AST >= 3x ULN and ALP <2x ULN and BIL >= 2x ULN)

2 participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Measure

TKI Cohort n=307 Participants 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.

Incidence of Hy's Law (ALT or AST >=3x ULN and ALP <2x ULN and BIL >=2x ULN)

1 participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	TKI Cohort n=101 Participants 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.
Maximum ALT Elevation Reached During Follow-up ALT: >=1x ULN to <3x ULN	82 participants
Maximum ALT Elevation Reached During Follow-up ALT: >=3x ULN to <5x ULN	8 participants
Maximum ALT Elevation Reached During Follow-up ALT: >=5x ULN to <10x ULN	10 participants
Maximum ALT Elevation Reached During Follow-up ALT: >=10x ULN to <20x ULN	0 participants
Maximum ALT Elevation Reached During Follow-up ALT: >=20x ULN	1 participants

SECONDARY outcome

Timeframe: 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.

Median time (in months) between index date and the date of maximum ALT elevation.

Outcome measures

Measure	TKI Cohort n=101 Participants 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.
Median Time to the Maximum ALT Elevation During Follow-up ALT: >=1x ULN to <3x ULN	4 months Interval 1.0 to 42.0
Median Time to the Maximum ALT Elevation During Follow-up ALT: >=3x ULN to <5x ULN	8 months Interval 0.0 to 17.0
Median Time to the Maximum ALT Elevation During Follow-up ALT: >=5x ULN to <10x ULN	3 months Interval 1.0 to 18.0
Median Time to the Maximum ALT Elevation During Follow-up ALT: >=10x ULN to <20x	0 months Interval 0.0 to 0.0
Median Time to the Maximum ALT Elevation During Follow-up ALT: >=20x ULN	7 months Interval 7.0 to 7.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	TKI Cohort n=101 Participants 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.
Maximum AST Elevation Reached During Follow-up AST: >=1x ULN to <3x ULN	87 participants
Maximum AST Elevation Reached During Follow-up AST: >=3x ULN to <5x ULN	8 participants
Maximum AST Elevation Reached During Follow-up AST: >=5x ULN to <10x ULN	3 participants
Maximum AST Elevation Reached During Follow-up AST: >=10x ULN to <20x ULN	2 participants
Maximum AST Elevation Reached During Follow-up AST: >=20x ULN	1 participants

SECONDARY outcome

Timeframe: 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.

Median time (in months) between index date and date of maximum AST elevation

Outcome measures

Measure	TKI Cohort n=101 Participants 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.
Median Time to the Maximum AST Elevation During Follow-up AST: >=1x ULN to <3x ULN	4 months Interval 0.0 to 50.0
Median Time to the Maximum AST Elevation During Follow-up AST: >=3x ULN to <5x ULN	5 months Interval 1.0 to 18.0
Median Time to the Maximum AST Elevation During Follow-up AST: >=5x ULN to <10x ULN	3 months Interval 1.0 to 17.0
Median Time to the Maximum AST Elevation During Follow-up AST: >=10x ULN to <20x ULN	7 months Interval 3.0 to 11.0
Median Time to the Maximum AST Elevation During Follow-up AST: >=20x ULN	7 months Interval 7.0 to 7.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	TKI Cohort n=75 Participants 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.
Maximum ALP Elevation Reached During Follow-up ALP: >=1x ULN to <2x ULN	61 participants
Maximum ALP Elevation Reached During Follow-up ALP: >=2x ULN to <3x ULN	7 participants
Maximum ALP Elevation Reached During Follow-up ALP: >=3x ULN to <5x ULN	4 participants
Maximum ALP Elevation Reached During Follow-up ALP: >=5x ULN to <10x ULN	3 participants
Maximum ALP Elevation Reached During Follow-up ALP: >=10x ULN	0 participants

SECONDARY outcome

Timeframe: 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.

Median time (in months) between index date and date of maximum ALP elevation

Outcome measures

Measure	TKI Cohort n=75 Participants 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.
Median Time to the Maximum ALP Elevation During Follow-up ALP: >=1x ULN to <2x ULN	5 months Interval 0.0 to 34.0
Median Time to the Maximum ALP Elevation During Follow-up ALP: >=2x ULN to <3x ULN	3 months Interval 0.0 to 5.0
Median Time to the Maximum ALP Elevation During Follow-up ALP: >=3x ULN to <5x ULN	11 months Interval 3.0 to 17.0
Median Time to the Maximum ALP Elevation During Follow-up ALP: >=5x ULN to <10x ULN	8 months Interval 3.0 to 11.0
Median Time to the Maximum ALP Elevation During Follow-up ALP: >=10x ULN	0 months Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	TKI Cohort n=70 Participants 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.
Maximum BIL Elevation Reached During Follow-up BIL: >=1x ULN to <1.5x ULN	46 participants
Maximum BIL Elevation Reached During Follow-up BIL: >=1.5x ULN to <2x ULN	9 participants
Maximum BIL Elevation Reached During Follow-up BIL: >=2x ULN to <5x ULN	8 participants
Maximum BIL Elevation Reached During Follow-up BIL: >=5x ULN to <10x ULN	4 participants
Maximum BIL Elevation Reached During Follow-up BIL: >=10x ULN	3 participants

SECONDARY outcome

Timeframe: 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.

Median time (in months) between index date and date of maximum BIL elevation

Outcome measures

Measure	TKI Cohort n=70 Participants 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.
Median Time to the Maximum BIL Elevation During Follow-up BIL: >=1x ULN to <1.5x ULN	3 months Interval 0.0 to 26.0
Median Time to the Maximum BIL Elevation During Follow-up BIL: >=1.5x ULN to <2x ULN	3 months Interval 0.0 to 33.0
Median Time to the Maximum BIL Elevation During Follow-up BIL: >=2x ULN to <5x ULN	4 months Interval 2.0 to 17.0
Median Time to the Maximum BIL Elevation During Follow-up BIL: >=5x ULN to <10x ULN	8 months Interval 5.0 to 11.0
Median Time to the Maximum BIL Elevation During Follow-up BIL: >=10x ULN	6 months Interval 2.0 to 18.0

Adverse Events

TKI Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER