Trial Outcomes & Findings for A Study of Erlotinib (Tarceva) in Participants With Non-Small Cell Lung Cancer (NSCLC) (NCT NCT02774278)

NCT ID: NCT02774278

Last Updated: 2016-08-08

Results Overview

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Clinical benefit is defined in the Outcome Measure 5.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

264 participants

Primary outcome timeframe

Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Results posted on

2016-08-08

Participant Flow

Participant milestones

Participant milestones
Measure
Erlotinib
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Overall Study
STARTED
264
Overall Study
Safety Analysis Population (SAP)
261
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
264

Reasons for withdrawal

Reasons for withdrawal
Measure
Erlotinib
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Overall Study
Lack of Efficacy
199
Overall Study
Death
29
Overall Study
Adverse event/intercurrent illness
16
Overall Study
Refused treatment/did not cooperate
9
Overall Study
Administrative reasons
6
Overall Study
Withdrawal by Subject
3
Overall Study
Protocol Violation
2

Baseline Characteristics

A Study of Erlotinib (Tarceva) in Participants With Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Erlotinib
n=264 Participants
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Age, Continuous
60.8 years
STANDARD_DEVIATION 10.47 • n=5 Participants
Sex: Female, Male
Female
80 Participants
n=5 Participants
Sex: Female, Male
Male
184 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Population: Primary analysis set (PAS) included all participants who provided evaluable tissue samples and were included in the primary Affymetrix efficacy analysis.

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Clinical benefit is defined in the Outcome Measure 5.

Outcome measures

Outcome measures
Measure
Erlotinib
n=102 Participants
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Number of Differentially Expressed Genes Associated With Clinical Benefit
0 genes

PRIMARY outcome

Timeframe: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Population: PAS participants who had EGFR mutation at baseline were included in this analysis.

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Number of participants with EGFR mutation (L858R/ exon 19 deletion) and who achieved clinical benefit status was reported. Clinical benefit is defined in the Outcome Measure 5.

Outcome measures

Outcome measures
Measure
Erlotinib
n=6 Participants
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Number of Epidermal Growth Factor Receptor (EGFR) Mutation Participants Who Achieved Clinical Benefit
6 participants

PRIMARY outcome

Timeframe: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Population: PAS participants who had KRAS mutation at baseline were included in this analysis.

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Number of participants with KRAS gene mutation and who achieved clinical benefit status was reported. Clinical benefit is defined in the Outcome Measure 5.

Outcome measures

Outcome measures
Measure
Erlotinib
n=10 Participants
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Number of KRAS Mutation Participants Who Achieved Clinical Benefit
4 participants

SECONDARY outcome

Timeframe: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Population: Analysis population included all enrolled participants.

Tumor response was defined as either a CR or a PR prior to failure (disease progression, death from any cause, or a second malignancy). CR was defined as the complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. PR was defined as a greater than or equal to 50 percent (%) reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks.

Outcome measures

Outcome measures
Measure
Erlotinib
n=264 Participants
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Percentage of Participants With Overall Response of Complete Response (CR) or Partial Response (PR) Using Response Evaluation Criteria in Solid Tumors (RECIST)
15.2 percentage of participants
Interval 11.1 to 20.1

SECONDARY outcome

Timeframe: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Population: Analysis population included all enrolled participants.

Clinical benefit was defined as either a CR, PR, or SD prior to failure (disease progression, death from any cause, or a second malignancy). CR: complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. PR: greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions. PD: unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure
Erlotinib
n=264 Participants
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Percentage of Participants With Clinical Benefit (CR, PR, or Stable Disease [SD] for at Least 12 Weeks After Study Entry) Using RECIST
31.4 percentage of participants
Interval 25.9 to 37.4

Adverse Events

Erlotinib

Serious events: 65 serious events
Other events: 209 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Erlotinib
n=261 participants at risk
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Respiratory, thoracic and mediastinal disorders
Dyspnoea
4.2%
11/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Haemoptysis
1.9%
5/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.77%
2/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Hydropneumothorax
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Pleural effusion
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Pneumothorax
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Infections and infestations
Pneumonia
4.6%
12/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Infections and infestations
Urinary tract infection
0.77%
2/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Infections and infestations
Bronchitis
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Infections and infestations
Lower respiratory tract infection
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Infections and infestations
Pneumonia staphylococcal
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Infections and infestations
Septic shock
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
Asthenia
1.1%
3/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
General physical health deterioration
1.1%
3/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
Pyrexia
1.1%
3/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
Fatigue
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
Gait disturbance
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Diarrhoea
1.1%
3/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Vomiting
0.77%
2/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Abdominal pain
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Dysphagia
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Gastric ulcer
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Cardiac disorders
Acute myocardial infarction
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Cardiac disorders
Cardiac failure congestive
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Cardiac disorders
Myocardial ischaemia
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Cardiac disorders
Pericarditis
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Nervous system disorders
Cerebral infarction
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Nervous system disorders
Cerebrovascular accident
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Nervous system disorders
Dizziness
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Nervous system disorders
Ischaemic stroke
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Blood and lymphatic system disorders
Anaemia
0.77%
2/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Blood and lymphatic system disorders
Haemorrhagic diathesis
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Metabolism and nutrition disorders
Dehydration
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Metabolism and nutrition disorders
Hypoglycaemia
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Metabolism and nutrition disorders
Hyponatraemia
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Skin and subcutaneous tissue disorders
Rash
0.77%
2/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Skin and subcutaneous tissue disorders
Skin ulcer haemorrhage
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Psychiatric disorders
Agitation
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Psychiatric disorders
Completed suicide
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Psychiatric disorders
Confusional state
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Vascular disorders
Arterial haemorrhage
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Vascular disorders
Shock
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Injury, poisoning and procedural complications
Fall
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Musculoskeletal and connective tissue disorders
Bone pain
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Renal and urinary disorders
Renal failure acute
0.38%
1/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.

Other adverse events

Other adverse events
Measure
Erlotinib
n=261 participants at risk
Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Skin and subcutaneous tissue disorders
Rash
51.0%
133/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Skin and subcutaneous tissue disorders
Dry skin
12.6%
33/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Skin and subcutaneous tissue disorders
Pruritus
12.3%
32/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Skin and subcutaneous tissue disorders
Acne
5.4%
14/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Diarrhoea
32.2%
84/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Vomiting
10.0%
26/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Gastrointestinal disorders
Nausea
8.8%
23/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Cough
14.9%
39/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Dyspnoea
14.2%
37/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Respiratory, thoracic and mediastinal disorders
Haemoptysis
5.7%
15/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
Fatigue
12.3%
32/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
General disorders
Pyrexia
5.4%
14/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.
Metabolism and nutrition disorders
Anorexia
15.7%
41/261 • Up to 4 years
Safety analysis population (SAP) included all participants who received at least one dose of the trial medication and had a safety follow-up.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

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