Non-Small Cell Lung Cancer
Conditions
Brief summary
This single arm, open-label study will assess the efficacy and safety of Tarceva (erlotinib) in patients with locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. Patients will receive Tarceva at a dose of 150 mg daily orally until disease progression or unacceptable toxicity occurs.
Interventions
DRUGerlotinib [Tarceva]
150 mg daily orally
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/=18 years of age * Locally advanced or metastatic (stage III/IV) non-small cell lung cancer with EGFR mutations * Measurable disease according to RECIST criteria * ECOG performance status 0-2 * Adequate haematological, renal and liver function
Exclusion criteria
* Previous chemotherapy or therapy against EGFR for metastatic disease * History of another malignancy, except for in situ carcinoma of the cervix, adequately treated basal cell skin carcinoma, or radically treated prostate carcinoma with good prognosis * Symptomatic cerebral metastases * Pre-existing parenchymal lung disease such as pulmonary fibrosis * Concomitant use of coumarins
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Among Erlotinib-Treated Participants With the EGFR Mutation | Per standard of care (every 3 months) until discontinuation for up to approximately 2 years | PFS was defined as the time from the first dose of erlotinib to the first documentation of disease progression or death, whichever occurred first. Tumor progression was determined using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which defines progression as a 20 percent (%) or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeters (mm), or the appearance of one or more new lesions. PFS was calculated in months as \[first event date minus first dose date plus 1\] divided by 30.44. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Erlotinib-Treated Participants With the EGFR Mutation With an Objective Response Per RECIST v1.1 | Per standard of care (every 3 months) until discontinuation for up to approximately 2 years | Objective tumor response was assessed by the investigator using RECIST v1.1 and recorded as complete response (CR), partial response (PR), or unmeasurable. RECIST v1.1 defines CR as disappearance of all target lesions, with short-axis reduction to less than (\<) 10 mm for any pathological lymph nodes, and PR as a 30% or greater reduction from baseline in the sum of diameters of target lesions. |
| Overall Survival (OS) Among Erlotinib-Treated and Untreated Participants | Per standard of care (every 3 months) until discontinuation for up to approximately 2 years | OS was defined as the time from recorded diagnosis to death from any cause or last patient last visit. OS was calculated in months as \[death date or last-known alive date minus diagnosis date plus 1\] divided by 30.44. |
| Percentage of Participants Alive at 6 and 12 Months | At 6 and 12 months | Death from any cause was documented at 6 and 12 months from recorded diagnosis. The percentage of participants alive at each timepoint was calculated as \[number of participants alive divided by number enrolled\] multiplied by 100. |
| Percentage of Participants With EGFR Mutation at Screening | Screening | Participants were tested at Screening for the presence of activating mutations in the tyrosine kinase domain of EGFR. The percentage of participants with mutation was calculated as \[number of mutation-positive participants divided by number tested\] multiplied by 100. |
Countries
Finland
Participant flow
Pre-assignment details
All participants underwent EGFR mutation testing at Screening. Those positive for the EGFR mutation and who met eligibility criteria (number of participants \[n\] = 3) received treatment with erlotinib. The remaining participants (n = 21) were followed for overall survival but did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants positive for the EGFR mutation and who met eligibility criteria received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. | 3 |
| Untreated Participants without the EGFR mutation were followed for overall survival but did not undergo treatment. Additionally, participants positive for the EGFR mutation who were excluded from treatment were followed for overall survival. | 21 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 12 |
| Overall Study | Lost to Follow-up | 1 | 6 |
| Overall Study | Protocol Violation | 0 | 3 |
Baseline characteristics
| Characteristic | Erlotinib | Untreated | Total |
|---|---|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 7.6 | 67 years STANDARD_DEVIATION 8.4 | 68 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 2 Participants | 13 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 8 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
Progression-Free Survival (PFS) Among Erlotinib-Treated Participants With the EGFR Mutation
PFS was defined as the time from the first dose of erlotinib to the first documentation of disease progression or death, whichever occurred first. Tumor progression was determined using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which defines progression as a 20 percent (%) or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeters (mm), or the appearance of one or more new lesions. PFS was calculated in months as \[first event date minus first dose date plus 1\] divided by 30.44.
Time frame: Per standard of care (every 3 months) until discontinuation for up to approximately 2 years
Population: All Participants Treated: All participants who received at least one dose of erlotinib were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Progression-Free Survival (PFS) Among Erlotinib-Treated Participants With the EGFR Mutation | 13.7 months |
Secondary
Number of Erlotinib-Treated Participants With the EGFR Mutation With an Objective Response Per RECIST v1.1
Objective tumor response was assessed by the investigator using RECIST v1.1 and recorded as complete response (CR), partial response (PR), or unmeasurable. RECIST v1.1 defines CR as disappearance of all target lesions, with short-axis reduction to less than (\<) 10 mm for any pathological lymph nodes, and PR as a 30% or greater reduction from baseline in the sum of diameters of target lesions.
Time frame: Per standard of care (every 3 months) until discontinuation for up to approximately 2 years
Population: All Participants Treated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Number of Erlotinib-Treated Participants With the EGFR Mutation With an Objective Response Per RECIST v1.1 | Partial response | 2 participants |
| Erlotinib | Number of Erlotinib-Treated Participants With the EGFR Mutation With an Objective Response Per RECIST v1.1 | Unmeasurable | 1 participants |
Secondary
Overall Survival (OS) Among Erlotinib-Treated and Untreated Participants
OS was defined as the time from recorded diagnosis to death from any cause or last patient last visit. OS was calculated in months as \[death date or last-known alive date minus diagnosis date plus 1\] divided by 30.44.
Time frame: Per standard of care (every 3 months) until discontinuation for up to approximately 2 years
Population: All Participants Enrolled: All erlotinib-treated participants who received at least one dose of erlotinib, in addition to all enrolled untreated participants, were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival (OS) Among Erlotinib-Treated and Untreated Participants | 17.8 months |
| Untreated | Overall Survival (OS) Among Erlotinib-Treated and Untreated Participants | 11.3 months |
Secondary
Percentage of Participants Alive at 6 and 12 Months
Death from any cause was documented at 6 and 12 months from recorded diagnosis. The percentage of participants alive at each timepoint was calculated as \[number of participants alive divided by number enrolled\] multiplied by 100.
Time frame: At 6 and 12 months
Population: All Participants Enrolled
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Percentage of Participants Alive at 6 and 12 Months | At 6 months | 100 percentage of participants |
| Erlotinib | Percentage of Participants Alive at 6 and 12 Months | At 12 months | 100 percentage of participants |
| Untreated | Percentage of Participants Alive at 6 and 12 Months | At 6 months | 67 percentage of participants |
| Untreated | Percentage of Participants Alive at 6 and 12 Months | At 12 months | 24 percentage of participants |
Secondary
Percentage of Participants With EGFR Mutation at Screening
Participants were tested at Screening for the presence of activating mutations in the tyrosine kinase domain of EGFR. The percentage of participants with mutation was calculated as \[number of mutation-positive participants divided by number tested\] multiplied by 100.
Time frame: Screening
Population: All Participants Enrolled
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With EGFR Mutation at Screening | 17 percentage of participants |