Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This study will assess potentially predictive markers of efficacy in participants with NSCLC receiving oral erlotinib (Tarceva) therapy. The anticipated time on study treatment is until disease progression, unacceptable toxicity or death.
Interventions
DRUGErlotinib
Erlotinib will be administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced NSCLC * Tumor accessible for biopsy by bronchoscopy * Disease progression following course of standard chemotherapy, or participants unwilling/unable to undergo chemotherapy
Exclusion criteria
* Unstable systemic disease * Any other malignancies in the last 5 years * Brain metastases * Previous treatment with therapy acting on the epidermal growth factor receptor (EGFR) axis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Differentially Expressed Genes Associated With Clinical Benefit | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 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. |
| Number of Epidermal Growth Factor Receptor (EGFR) Mutation Participants Who Achieved Clinical Benefit | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 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. |
| Number of KRAS Mutation Participants Who Achieved Clinical Benefit | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response of Complete Response (CR) or Partial Response (PR) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 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. |
| Percentage of Participants With Clinical Benefit (CR, PR, or Stable Disease [SD] for at Least 12 Weeks After Study Entry) Using RECIST | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 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. |
Countries
Belgium, Bulgaria, Estonia, France, Germany, Hong Kong, Ireland, Italy, Poland, Russia, Singapore, Spain, Taiwan, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Erlotinib was administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death. | 264 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reasons | 6 |
| Overall Study | Adverse event/intercurrent illness | 16 |
| Overall Study | Death | 29 |
| Overall Study | Lack of Efficacy | 199 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Refused treatment/did not cooperate | 9 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 10.47 |
| Sex: Female, Male Female | 80 Participants |
| Sex: Female, Male Male | 184 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 209 / 261 |
| serious Total, serious adverse events | 65 / 261 |
Outcome results
Primary
Number of Differentially Expressed Genes Associated With Clinical Benefit
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Number of Differentially Expressed Genes Associated With Clinical Benefit | 0 genes |
Primary
Number of Epidermal Growth Factor Receptor (EGFR) Mutation Participants Who Achieved Clinical Benefit
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Number of Epidermal Growth Factor Receptor (EGFR) Mutation Participants Who Achieved Clinical Benefit | 6 participants |
Primary
Number of KRAS Mutation Participants Who Achieved Clinical Benefit
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Number of KRAS Mutation Participants Who Achieved Clinical Benefit | 4 participants |
Secondary
Percentage of Participants With Clinical Benefit (CR, PR, or Stable Disease [SD] for at Least 12 Weeks After Study Entry) Using RECIST
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.
Time frame: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | 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 |
Secondary
Percentage of Participants With Overall Response of Complete Response (CR) or Partial Response (PR) Using Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Time frame: Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years
Population: Analysis population included all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | 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 |