Non-Small Cell Lung Cancer
Conditions
Brief summary
This open-label, randomized, parallel arm study assessed the efficacy and safety of Tarceva (erlotinib) versus gemcitabine/cisplatin combination chemotherapy as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations in their tumours. Patients were randomized to receive either Tarceva 150 mg orally daily or 3-week cycles of gemcitabine 1250 mg/m\^2 intravenously (iv) on Days 1 and 8 plus cisplatin 75 mg/m\^2 iv on Day 1.
Interventions
DRUGErlotinib
Erlotinib was supplied as tablets.
DRUGChemotherapy
Cisplatin and gemcitabine were locally sourced with commercial products.
Sponsors
Hoffmann-La Roche
Study design
Allocation
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 participants, ≥ 18 years of age. * Locally advanced or recurrent (stage IIIB) or metastatic (stage IV) non-small cell lung cancer. * Presence of epidermal growth factor receptor (EGFR) mutations in tumours. * Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. * European Cooperative Oncology Group (ECOG) performance status ≤ 2.
Exclusion criteria
* Prior exposure to agents directed at the human epidermal receptor (HER) axis (eg, but not limited to erlotinib, gefitinib, cetuximab, or trastuzumab). * Prior chemotherapy or systemic anti-neoplastic therapy for advanced disease. * Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or active gastroduodenal ulcer disease. * Any inflammatory changes of the surface of the eye. * ≥ Grade 2 peripheral neuropathy. * History of any other malignancies within 5 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer. * Brain metastasis or spinal cord compression that has not yet been definitely treated with surgery and/or radiation, or treated but without evidence of stable disease for at least 2 months. * Human immunodeficiency virus (HIV) infection. * Pregnant, nursing, or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Duration of Progression-free Survival | Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months) | The duration of progression-free survival was defined as the time from randomization to disease progression (PD) or death from any cause, whichever occurs first. PD was defined as: (1) At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (2) An unequivocal progression of existing non-target lesions. When the patient has measurable disease, the overall tumor burden must have increased sufficiently to merit discontinuation of therapy. When the patient has only non-measurable disease, the increase in overall disease burden should be comparable in magnitude to the increase that would be required to declare PD for measurable disease. (3) The appearance of new malignant lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Control | Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) | A participant with disease control was defined as a participant with either a complete response (CR), a partial response (PR), or stable disease (SD), as determined using RECIST v1.1. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter of TLs taking as reference the Baseline sum longest diameter (SLD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. A SLD for all TLs will be calculated and reported as the Baseline SLD. |
| Duration of Response | Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) | Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. |
| Percentage of Responders as Assessed by the Investigator | Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) | A responder was defined as a participant with either a complete response (CR) or a partial response (PR), as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A CR was defined as: (1) The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \< 10 mm. (2) The disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be non-pathological in size (\< 10 mm in the short axis). A PR was defined as: (1) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (2) The persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits. |
| Safety: Incidence of Adverse Events | 36 months | — |
| Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire | approximately 21 months | — |
| Overall Survival | Baseline to the end of the study (3 years, 1 month) | Overall survival was defined as the time from the date of randomization to the date of death from any cause. |
Countries
China, Malaysia, Philippines
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity. | 110 |
| Chemotherapy Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first. | 107 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 58 | 57 |
| Overall Study | Lost to Follow-up | 5 | 3 |
| Overall Study | Other Reasons- Unspecified | 44 | 38 |
| Overall Study | Withdrawal by Subject | 2 | 9 |
Baseline characteristics
| Characteristic | Erlotinib | Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 10.37 | 55.8 years STANDARD_DEVIATION 10.41 | 56.3 years STANDARD_DEVIATION 10.37 |
| Sex: Female, Male Female | 68 Participants | 65 Participants | 133 Participants |
| Sex: Female, Male Male | 42 Participants | 42 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 99 / 110 | 96 / 104 |
| serious Total, serious adverse events | 22 / 110 | 16 / 104 |
Outcome results
Primary
Investigator-assessed Duration of Progression-free Survival
The duration of progression-free survival was defined as the time from randomization to disease progression (PD) or death from any cause, whichever occurs first. PD was defined as: (1) At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (2) An unequivocal progression of existing non-target lesions. When the patient has measurable disease, the overall tumor burden must have increased sufficiently to merit discontinuation of therapy. When the patient has only non-measurable disease, the increase in overall disease burden should be comparable in magnitude to the increase that would be required to declare PD for measurable disease. (3) The appearance of new malignant lesions.
Time frame: Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months)
Population: Full analysis set: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Investigator-assessed Duration of Progression-free Survival | 11.0 Months |
| Chemotherapy | Investigator-assessed Duration of Progression-free Survival | 5.5 Months |
Secondary
Duration of Response
Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.
Time frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Population: Full analysis set: All randomized participants. Only participants who had a complete response or partial response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Duration of Response | 10.8 Months |
| Chemotherapy | Duration of Response | 4.2 Months |
Secondary
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Time frame: Baseline to the end of the study (3 years, 1 month)
Population: Full analysis set: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival | 28.9 Months |
| Chemotherapy | Overall Survival | 27.1 Months |
Secondary
Percentage of Participants With Disease Control
A participant with disease control was defined as a participant with either a complete response (CR), a partial response (PR), or stable disease (SD), as determined using RECIST v1.1. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter of TLs taking as reference the Baseline sum longest diameter (SLD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. A SLD for all TLs will be calculated and reported as the Baseline SLD.
Time frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Population: Full analysis set: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With Disease Control | 91.8 Percentage of participants |
| Chemotherapy | Percentage of Participants With Disease Control | 82.2 Percentage of participants |
Secondary
Percentage of Responders as Assessed by the Investigator
A responder was defined as a participant with either a complete response (CR) or a partial response (PR), as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A CR was defined as: (1) The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \< 10 mm. (2) The disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be non-pathological in size (\< 10 mm in the short axis). A PR was defined as: (1) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (2) The persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits.
Time frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Population: Full analysis set: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Responders as Assessed by the Investigator | 68.2 Percentage of responders |
| Chemotherapy | Percentage of Responders as Assessed by the Investigator | 39.3 Percentage of responders |
Secondary
Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire
Time frame: approximately 21 months
Secondary
Safety: Incidence of Adverse Events
Time frame: 36 months