Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (TRIGGER) (NCT NCT01378962)

Last Updated: 2018-01-23

Results Overview

According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

12 months

Results posted on

2018-01-23

Participant Flow

Participant milestones

Participant milestones
Measure	Erlotinib 150 mg Erlotinib 150 milligrams (mg) tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Overall Study STARTED	50
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib 150 mg Erlotinib 150 milligrams (mg) tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Overall Study Death	14
Overall Study Lost to Follow-up	1
Overall Study Other	2

Baseline Characteristics

A Study of Tarceva (Erlotinib) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (TRIGGER)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Age, Continuous	62.86 years STANDARD_DEVIATION 11.42 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Intent to treat (ITT) population included all participants enrolled in the study who received at least 1 dose of treatment.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants With Disease Progression or Death at 12 Months After Baseline	42 percentage of participants

PRIMARY outcome

Timeframe: Up to 1 year after enrollment of the last participant (maximum up to 27 months)

Population: ITT population.

PFS was defined as the time from baseline to the date of first occurrence of disease progression or death. According to RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. PFS was assessed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Progression-Free Survival (PFS)	12.58 months Interval 10.25 to 16.95

PRIMARY outcome

Timeframe: 12 months

Population: ITT population.

According to RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Probability of Being Progression Free 12 Months After Baseline	0.51 probability of being progression-free Standard Error 0.08

SECONDARY outcome

Timeframe: Every 8 weeks during treatment, after discontinuation participants were followed for up to 1 year after enrollment of the last participant (maximum up to 27 months)

Population: ITT population.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants Who Died	28 percentage of participants

SECONDARY outcome

Timeframe: Every 8 weeks during treatment, after discontinuation participants were followed for up to 1 year after enrollment of the last participant (maximum up to 27 months)

Population: ITT population.

OS was defined as the time from randomization to the date of death due to any cause. OS was assessed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Overall Survival (OS)	17.48 months Standard Error 1.09

SECONDARY outcome

Timeframe: Baseline up to disease progression or end of study (up to 12 Months)

Population: ITT population.

Tumor response was assessed according to RECIST v1.1. Complete response (CR): complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes must decrease to normal (short axis less than 10 mm), with no new lesions. Partial response (PR): greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. PD: \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Stable disease (SD): not qualifying for CR, PR, or PD.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants With a Response by Best Overall Response CR	6 percentage of participants
Percentage of Participants With a Response by Best Overall Response PR	62 percentage of participants
Percentage of Participants With a Response by Best Overall Response SD	12 percentage of participants
Percentage of Participants With a Response by Best Overall Response PD	4 percentage of participants
Percentage of Participants With a Response by Best Overall Response Not estimated	16 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to disease progression or end of study (up to 12 Months)

Population: ITT population.

Objective response was defined as the percentage of participants with CR or PR as best overall response by RECIST v1.1. To be assigned the status of PR or CR, changes in tumor measurements were to be confirmed by repeated assessments no less than 4 weeks after the criteria for response were first met. CR was defined as complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than 10 mm), with no new lesions. PR was defined as \>=30% decrease under baseline of sum of diameters of all target lesions. The short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. Participants with no tumor assessment after start of study treatment were considered as non-responders. The percentage of participants with response is presented.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants With Objective Response	68 percentage of participants Interval 53.0 to 80.0

SECONDARY outcome

Timeframe: Baseline up to disease progression or end of study (up to 12 Months)

Population: ITT population.

The Disease Control Rate was defined as the percentage of participants who had CR or PR or SD as Best Overall Response achieved within the time between the first drug administration and documented disease progression or end of study. According to RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than 10 mm), with no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. SD was defined as not qualifying for CR, PR, or PD.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=50 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants Achieving CR, PR, or SD as Best Overall Response	80 percentage of participants Interval 66.0 to 90.0

SECONDARY outcome

Timeframe: Baseline up to disease progression (up to 12 Months)

Population: Analysis population included all participants enrolled in the study who received at least 1 dose of treatment and who had a documented PD response during the study period.

Primary resistance: participants did not reach SD or PR or CR before going to PD. Secondary resistance: participants experienced PD after having reached SD or PR or CR at least once. CR: complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes must decrease to normal (short axis less than 10 mm), with no new lesions. PR: \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. PD: \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=24 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants With Primary and Secondary Resistance Primary resistance	8.33 percentage of participants
Percentage of Participants With Primary and Secondary Resistance Secondary resistance	91.67 percentage of participants

SECONDARY outcome

Timeframe: Baseline, At progression of disease (up to 12 Months)

Population: Analysis population included all participants enrolled in the study who received at least 1 dose of treatment and who had samples for EGFR mutation. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed at specified time point.

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR mutation was determined in liquid biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR /Cobas).

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=45 Participants Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type At PD: EGFR18 Mutation (n=18)	0.00 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type Baseline: EGFR18 Mutation (n=45)	0.00 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type Baseline: EGFR19 Codon Deletion Mutation (n=45)	51.11 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type Baseline: EGFR20 Codon T790M Mutation (n=45)	2.22 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type Baseline: EGFR21 Codon L585R Mutation (n=45)	15.56 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type At PD: EGFR19 Codon Deletion Mutation (n=18)	50.00 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type At PD: EGFR20 Codon T790M Mutation (n=18)	27.78 percentage of participants
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type At PD: EGFR21 Codon L585R Mutation (n=18)	16.67 percentage of participants

Adverse Events

Erlotinib 150 mg

Serious events: 10 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Erlotinib 150 mg n=50 participants at risk Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Cardiac disorders Cardiac failure acute	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Gastrointestinal disorders Dysphagia	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
General disorders Chest pain	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Infections and infestations Pneumonia	4.0% 2/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Injury, poisoning and procedural complications Hip fracture	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Metabolism and nutrition disorders Decreased appetite	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Nervous system disorders Convulsion	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Nervous system disorders Hemiplegia	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Psychiatric disorders Confusional state	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.0% 2/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Vascular disorders Jugular vein thrombosis	2.0% 1/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.

Other adverse events

Other adverse events
Measure	Erlotinib 150 mg n=50 participants at risk Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
Ear and labyrinth disorders Vertigo	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Eye disorders Conjunctivitis	22.0% 11/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Gastrointestinal disorders Abdominal pain upper	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Gastrointestinal disorders Diarrhoea	54.0% 27/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Gastrointestinal disorders Stomatitis	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Gastrointestinal disorders Vomiting	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
General disorders Asthenia	18.0% 9/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
General disorders Chest pain	14.0% 7/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
General disorders Fatigue	10.0% 5/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
General disorders Pyrexia	18.0% 9/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Infections and infestations Paronychia	14.0% 7/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Injury, poisoning and procedural complications Contrast media reaction	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Investigations Blood bilirubin increased	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Metabolism and nutrition disorders Decreased appetite	12.0% 6/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Musculoskeletal and connective tissue disorders Back pain	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 10/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Alopecia	14.0% 7/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Dermatitis acneiform	10.0% 5/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Dry skin	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Pruritus	20.0% 10/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Rash	72.0% 36/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Skin ulcer	8.0% 4/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Gastrointestinal disorders Nausea	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
General disorders Oedema peripheral	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Infections and infestations Cystitis	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
Skin and subcutaneous tissue disorders Nail disorder	6.0% 3/50 • Up to 1 year after enrollment of the last participant (maximum up to 27 months) Safety population included all participants enrolled in the study who received at least one dose of treatment and had at least one safety assessment.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER