Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This open-label, non-randomized, one-arm study will evaluate the safety and efficacy of Tarceva (erlotinib) as single-agent first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer who show epidermal growth factor receptor (EGFR) activating mutations. Patients will receive Tarceva 150 mg orally daily until disease progression or unacceptable toxicity occurs.
Interventions
DRUGerlotinib [Tarceva]
150 mg orally daily, until disease progression, unacceptable toxicity or withdrawal due to any reason
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
* Adult patients, \>/= 18 years of age * Histologically or cytologically documented, inoperable, locally advanced, recurrent or metastatic (Stage IIIB or Stage IV) lung adenocarcinoma * Non-small cell lung cancer with an EGFR activating mutation * Patients must have evidence of disease, but measurable disease is not mandatory * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate renal and liver function
Exclusion criteria
* Prior chemotherapy or other systemic anti-cancer treatment. Neoadjuvant/adjuvant chemotherapy is allowed if completed within 6 months prior to enrolment. Prior radiochemotherapy is allowed if completed more than 6 months before start of study treatment * Prior therapy with systemic anti-tumour therapy with HER1/EGFR inhibitors * Any other malignancies within 5 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin carcinoma * Brain metastasis or spinal cord compression not yet definitely treated with surgery and/or radiation * Patients unable to take oral medication or requiring intravenous alimentation, with prior surgical procedures affecting absorption or active peptic ulcer disease * Any significant ophthalmologic abnormality, especially those likely to increase the risk of corneal epithelial lesions; the use of contact lenses is not recommended during the study * Pregnant or breast-feeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline to progressive disease or death (up to 34 months) | PFS was defined as median time from the first dose of study treatment to the first documentation of objective tumor progression (according to Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1) or to death due to any cause, whichever occurred first. Progressive Disease (PD) was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. Median and the 95% confidence interval were estimated using Kaplan-Meier survival methodology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Overall Response (BOR) | Baseline to progressive disease or death (up to 34 months) | BOR was defined as best tumor response (as per RECIST version 1.1) recorded for a participant during the study. Complete Response (CR): disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than \[\<\] 10 millimeters \[mm\] short axis). Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Percentage of Participants Who Were Alive at 1 Year | 1 Year (12 months) | — |
Countries
Hungary, Latvia, Turkey (Türkiye)
Participant flow
Pre-assignment details
A total of 651 participants were screened and among them 62 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Hydrochloride Participants received a single 150 mg oral dose of erlotinib hydrochloride tablet daily from Day 1 until disease progression, death, unacceptable toxicity or consent withdrawal, whichever occurred first up to 34 months. | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 7 |
| Overall Study | Disease Progression | 28 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Erlotinib Hydrochloride |
|---|---|
| Age, Continuous | 67.69 Years STANDARD_DEVIATION 10.562 |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 49 / 62 |
| serious Total, serious adverse events | 26 / 62 |
Outcome results
Primary
Progression-Free Survival (PFS)
PFS was defined as median time from the first dose of study treatment to the first documentation of objective tumor progression (according to Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1) or to death due to any cause, whichever occurred first. Progressive Disease (PD) was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. Median and the 95% confidence interval were estimated using Kaplan-Meier survival methodology.
Time frame: Baseline to progressive disease or death (up to 34 months)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib Hydrochloride | Progression-Free Survival (PFS) | 12.846 Months |
Secondary
Percentage of Participants Who Were Alive at 1 Year
Time frame: 1 Year (12 months)
Population: ITT population. Here, number of participants analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib Hydrochloride | Percentage of Participants Who Were Alive at 1 Year | 82.5 Percentage of Participants |
Secondary
Percentage of Participants With Best Overall Response (BOR)
BOR was defined as best tumor response (as per RECIST version 1.1) recorded for a participant during the study. Complete Response (CR): disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than \[\<\] 10 millimeters \[mm\] short axis). Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Baseline to progressive disease or death (up to 34 months)
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib Hydrochloride | Percentage of Participants With Best Overall Response (BOR) | SD | 32.1 Percentage of Participants |
| Erlotinib Hydrochloride | Percentage of Participants With Best Overall Response (BOR) | PD | 1.8 Percentage of Participants |
| Erlotinib Hydrochloride | Percentage of Participants With Best Overall Response (BOR) | PR | 64.3 Percentage of Participants |
| Erlotinib Hydrochloride | Percentage of Participants With Best Overall Response (BOR) | CR | 1.8 Percentage of Participants |