Breast Neoplasms
Conditions
Brief summary
The general aim of this study is to investigate the efficacy and safety of afatinib (BIBW 2992) alone and in combination with weekly paclitaxel or weekly vinorelbine (in patients who progress on afatinib monotherapy within this trial) as treatment in patients with HER2-overexpressing, metastatic breast cancer, who failed HER2-targeted treatment in the neoadjuvant or adjuvant setting
Interventions
DRUGVinorelbine 25 mg/m2 weekly
Patients to additionally receive vinorelbine at a dose of 25 mg/m2 weekly on disease progression on afatinib monotherapy
DRUGAfatinib 40mg once daily (OD)
Patient to receive afatinib monotherapy at a dose of 40 mg/d until progression of their disease
Patients to additionally receive paclitaxel at a dose of 80 mg/m2 weekly on disease progression on afatinib monotherapy
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female patients \>=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer 2. Stage IV metastatic disease 3. At least one measurable lesion according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1). Skin, bone and brain lesions are considered non-target lesions 4. Must have failed or progressed on either trastuzumab or lapatinib or trastuzumab and lapatinib treatment in the neoadjuvant and/or adjuvant setting
Exclusion criteria
1. Prior first line therapy for metastatic breast cancer 2. Known pre-existing interstitial lung disease 3. Active brain metastases 4. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to trial treatment. 5. Cardiac left ventricular function with resting ejection fraction of less than 50%. 6. Prior treatment with Epidermal Growth Factor Receptor (EGFR)/HER2-targeted small molecules or antibodies other than trastuzumab and lapatinib in the neoadjuvant or adjuvant setting 7. Prior treatment with paclitaxel in the past 12 months 8. Must not have received prior vinorelbine treatment - Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1 | From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days | Objective response according to RECIST v1.1. Best overall response of confirmed complete response (CR) or confirmed partial response (PR) recorded since first administration of trial medication and until the earliest of disease progression, death or start of next treatment in each part separately. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of participants with OR along with exact 95% Confidence Interval by Clopper and Pearson is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days | Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part (without clinical disease assessment) .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
| Progression Free Survival (PFS) | From drug start date in monotherapy to 1st disease progression and drug start date in combination therapy to 2nd disease progression | Progression Free Survival is defined as the time from the drug start date to the date of 1st disease progression or death for monotherapy and 2nd disease progression or death from the drug start date of the combination therapy for combination therapy'. Median is calculated from the Kaplan-Meier curve. |
| Duration of Objective Response According to RECIST v1.1 | From the first objective response to the time of progression or death, up to 1562 days | Duration of objective response, defined as the time from first objective response to the time of progression or death. (regardless of confirmation). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
| Best Overall Response According to RECIST v1.1 (With Confirmation) | From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days | Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
| Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) | Baseline and End of treatment period, up to 1562 days | Change from baseline to end of treatment in systolic blood pressure (SBP). |
| Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP) | Baseline and End of treatment period, up to 1562 days | Change from baseline to end of treatment in diastolic blood pressure (DBP). |
| Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days | Number of patient with possibly clinically significant (PCS) laboratory values by functional group (haematology, differentials, coagulation, electrolytes, enzymes, and substrates). Acronyms Used: Prothrombin time-International normalized ratio (PT-INR), Alanine aminotransferase/Glutamic pyruvic transaminase (ALT/GPT) Serum glutamic pyruvic transaminase (SGPT), Aspartate aminotransferase/Glutamic-oxaloacetic transaminase (AST/GOT) Serum glutamic-oxaloacetic transaminase (SGOT) |
| Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher | From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days | Percentage of patients with highest common terminology criteria for adverse events (CTCAE) version 3.0 Grade of 3 or higher. |
Countries
Hong Kong, India, Poland, Russia, Taiwan, United Kingdom
Participant flow
Recruitment details
An open-label, multinational, phase-II trial of Afatinib (BIBW 2992) in patients with metastatic human epidermal growth factor receptor (HER2) - overexpressing breast cancer failing HER2 - targeted treatment in the neoadjuvant and/or adjuvant treatment setting
Pre-assignment details
All subjects were screened for eligibility. It was not planned to compare efficacy of the combination therapies Afatinib and Paclitaxel or Afatinib and Vinorelbine as the study was stopped prematurely and the patient number in both treatment groups is not significant. However, for safety reporting both combination therapy are reported separately
Participants by arm
| Arm | Count |
|---|---|
| Afatinib Monotherapy Patient received Afatinib monotherapy orally once daily at a dose of 40 milligram (mg) film-coated tablets until progression of their disease, unacceptable adverse events or other reason necessitating withdrawal. Patients could have dose reduced if 40 mg was not tolerated. | 74 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A | Clinical signs/symptoms of progression | 2 | 0 |
| Part A | Lost to Follow-up | 1 | 0 |
| Part A | Other Adverse Event | 8 | 0 |
| Part A | Other than specified | 3 | 0 |
| Part A | Progressive disease according to RECIST | 8 | 0 |
| Part A | Protocol Violation | 1 | 0 |
| Part A | Withdrawal by Subject | 12 | 0 |
| Part B | Clinical signs/symptoms of progression | 0 | 2 |
| Part B | Other Adverse Event | 0 | 1 |
| Part B | Other than specified | 0 | 2 |
| Part B | Protocol Violation | 0 | 1 |
| Part B | Withdrawal by Subject | 0 | 6 |
Baseline characteristics
| Characteristic | Afatinib Monotherapy |
|---|---|
| Age, Continuous | 51.3 Years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 47 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 74 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 74 | 1 / 13 | 5 / 26 |
| other Total, other adverse events | 67 / 74 | 13 / 13 | 23 / 26 |
| serious Total, serious adverse events | 18 / 74 | 5 / 13 | 10 / 26 |
Outcome results
Primary
Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1
Objective response according to RECIST v1.1. Best overall response of confirmed complete response (CR) or confirmed partial response (PR) recorded since first administration of trial medication and until the earliest of disease progression, death or start of next treatment in each part separately. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of participants with OR along with exact 95% Confidence Interval by Clopper and Pearson is presented.
Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. Treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel or of afatinib and vinorelbine. It was not planned to compare between the two types of combination therapies hence arm is combined
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib Monotherapy | Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1 | 18 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Percentage of Participants With Objective Response (OR) Assessed by Response Evaluation Criteria in Solid Tumours Version (RECIST) 1.1 | 31 Percentage of participants |
Secondary
Best Overall Response According to RECIST v1.1 (Regardless of Confirmation)
Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part (without clinical disease assessment) .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. Treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel or of afatinib and vinorelbine. It was not planned to compare between the two types of combination therapies hence arm is combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Partial response (PR) | 19 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Progressive disease | 28 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Stable disease (SD) | 42 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Not evaluable | 9 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Complete response (CR) | 1 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Not evaluable | 13 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Complete response (CR) | 0 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Partial response (PR) | 44 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Stable disease (SD) | 33 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (Regardless of Confirmation) | Progressive disease | 10 Percentage of participants |
Secondary
Best Overall Response According to RECIST v1.1 (With Confirmation)
Best overall response was assessed according to RECIST version 1.1 and was calculated relative to the baseline of each respective part .Percentage of participants with best overall response along with exact 95% Confidence Interval by Clopper and Pearson is presented. Best overall response was defined as the best response recorded at any time from the first administration of drug to the End of Treatment (EOT). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. Treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel or of afatinib and vinorelbine. It was not planned to compare between the two types of combination therapies hence arm is combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Partial response (PR) | 16 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Progressive disease | 28 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Stable disease (SD) | 45 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Not evaluable | 9 Percentage of participants |
| Afatinib Monotherapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Complete response (CR) | 1 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Not evaluable | 13 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Complete response (CR) | 0 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Partial response (PR) | 31 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Stable disease (SD) | 46 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Best Overall Response According to RECIST v1.1 (With Confirmation) | Progressive disease | 10 Percentage of participants |
Secondary
Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP)
Change from baseline to end of treatment in diastolic blood pressure (DBP).
Time frame: Baseline and End of treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. The treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel, or of afatinib and vinorelbine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Afatinib Monotherapy | Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP) | -1.8 Millimeter of mercury (mmHg) | Standard Deviation 12 |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP) | 1.9 Millimeter of mercury (mmHg) | Standard Deviation 10.7 |
| Afatinib and Paclitaxel Combination Therapy | Change From Baseline to End of Treatment in Diastolic Blood Pressure (DBP) | -1.6 Millimeter of mercury (mmHg) | Standard Deviation 10 |
Secondary
Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP)
Change from baseline to end of treatment in systolic blood pressure (SBP).
Time frame: Baseline and End of treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. The treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel, or of afatinib and vinorelbine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Afatinib Monotherapy | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) | -1.2 Millimeter of mercury (mmHg) | Standard Deviation 17.9 |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) | -1.0 Millimeter of mercury (mmHg) | Standard Deviation 15.1 |
| Afatinib and Paclitaxel Combination Therapy | Change From Baseline to End of Treatment in Systolic Blood Pressure (SBP) | -3.7 Millimeter of mercury (mmHg) | Standard Deviation 12.1 |
Secondary
Duration of Objective Response According to RECIST v1.1
Duration of objective response, defined as the time from first objective response to the time of progression or death. (regardless of confirmation). As Per RECIST v1.1 for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; progression, at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: From the first objective response to the time of progression or death, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. Treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel or of afatinib and vinorelbine. It was not planned to compare between the two types of combination therapies hence arm is combined
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Afatinib Monotherapy | Duration of Objective Response According to RECIST v1.1 | 168.5 Days |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Duration of Objective Response According to RECIST v1.1 | 125.0 Days |
Secondary
Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values
Number of patient with possibly clinically significant (PCS) laboratory values by functional group (haematology, differentials, coagulation, electrolytes, enzymes, and substrates). Acronyms Used: Prothrombin time-International normalized ratio (PT-INR), Alanine aminotransferase/Glutamic pyruvic transaminase (ALT/GPT) Serum glutamic pyruvic transaminase (SGPT), Aspartate aminotransferase/Glutamic-oxaloacetic transaminase (AST/GOT) Serum glutamic-oxaloacetic transaminase (SGOT)
Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. Number Analyzed are the patients with no possible clinically significant abnormality at baseline. Treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel, or of afatinib and vinorelbine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Substrates - Creatinine (high) | 0 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - AST/GOT SGOT (high) | 8 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Potassium (low) | 3 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - Platelets (low) | 2 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Magnesium (low) | 0 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Potassium (high) | 2 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - Haemoglobin (low) | 9 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - White blood cell count (low) | 5 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - Alkaline phosphatase (high) | 6 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Differentials, automatic - Neutrophils (low) | 1 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Substrates - Bilirubin, total (high) | 2 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - ALT/GPT SGPT (high) | 6 Participants |
| Afatinib Monotherapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Coagulation - PT-INR (high) | 1 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Potassium (high) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - Haemoglobin (low) | 5 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - White blood cell count (low) | 9 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - Platelets (low) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Differentials, automatic - Neutrophils (low) | 10 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Coagulation - PT-INR (high) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Potassium (low) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Magnesium (low) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - AST/GOT SGOT (high) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - ALT/GPT SGPT (high) | 3 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - Alkaline phosphatase (high) | 1 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Substrates - Creatinine (high) | 0 Participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Substrates - Bilirubin, total (high) | 1 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - AST/GOT SGOT (high) | 2 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Differentials, automatic - Neutrophils (low) | 12 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Substrates - Creatinine (high) | 1 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - ALT/GPT SGPT (high) | 4 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - Platelets (low) | 1 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - Haemoglobin (low) | 17 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Enzymes - Alkaline phosphatase (high) | 2 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Potassium (high) | 0 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Potassium (low) | 3 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Haematology - White blood cell count (low) | 13 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Electrolytes - Magnesium (low) | 1 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Coagulation - PT-INR (high) | 0 Participants |
| Afatinib and Paclitaxel Combination Therapy | Number of Patient With Possibly Clinically Significant (PCS) Laboratory Values | Substrates - Bilirubin, total (high) | 0 Participants |
Secondary
Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher
Percentage of patients with highest common terminology criteria for adverse events (CTCAE) version 3.0 Grade of 3 or higher.
Time frame: From the initial dose of study drug until 28 days after end of the treatment period, up to 1562 days
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. The treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel, or of afatinib and vinorelbine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib Monotherapy | Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher | 43 Percentage of participants |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher | 62 Percentage of participants |
| Afatinib and Paclitaxel Combination Therapy | Percentage of Patients With Highest Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade of 3 or Higher | 65 Percentage of participants |
Secondary
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from the drug start date to the date of 1st disease progression or death for monotherapy and 2nd disease progression or death from the drug start date of the combination therapy for combination therapy'. Median is calculated from the Kaplan-Meier curve.
Time frame: From drug start date in monotherapy to 1st disease progression and drug start date in combination therapy to 2nd disease progression
Population: The treated set for monotherapy comprised all patients who received at least 1 dose of afatinib. Treated set for combination therapy comprised all patients who received at least 1 dose of each of afatinib and paclitaxel or of afatinib and vinorelbine. It was not planned to compare between the two types of combination therapies hence arm is combined
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Afatinib Monotherapy | Progression Free Survival (PFS) | 86.0 Days |
| Afatinib and Paclitaxel or Vinorelbine Combination Therapy | Progression Free Survival (PFS) | 135.0 Days |