Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Non-Small Cell Lung Cancer (NSCLC), Sorafenib
Brief summary
The purpose of the study is to see if sorafenib plus best supportive care (i.e. in addition to the non-cancer treatments patients would normally receive) is an effective treatment for lung cancer compared to best supportive care alone. The safety and tolerability of the two treatment groups will also be compared. The goal of the study is to test the ability of sorafenib to improve survival compared to best supportive care alone.
Detailed description
Acronyms used in Adverse Events section: Disseminated intravascular coagulation (DIC), International normalized ratio (INR), Atrioventricular (AV), Gastrointestinal (GI), Not otherwise specified (NOS), Common Terminology Criteria for Adverse Events (CTCAE), Absolute neutrophil count (ANC), Central nervous system (CNS), Acute respiratory distress syndrome (ARDS), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST).
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg twice daily (BID)
DRUGPlacebo
Placebo - 2 tablets twice daily (BID)
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and willingness to sign a written Informed Consent * Advanced relapsed or refractory predominantly non squamous NSCLC. The diagnosis must have been confirmed cyto-/ histologically * Patients must have measurable or non-measurable disease * At least two but not more than three prior standard treatment regimens for NSCLC * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Male or female subjects \>/= 18 years of age (\>/=20 for Japan) at the time of Informed Consent * Life expectancy of at least 12 weeks * Ability to swallow oral medication * Both men and women using adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of the study drug: * Haemoglobin \> 9.0 g/dl * Absolute neutrophil count (ANC) \>1,500/mm3 * Platelet count \>/= 100,000/µl * Total bilirubin \</=1.5 x the upper limit of normal * Alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (\</= 5 x upper limit of normal in patients with liver metastases) Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (\</= 5 x upper limit of normal in patients with liver metastases) * Alkaline phosphatase \< 4 x upper limit of normal (\</= 5 x upper limit of normal in patients with liver metastases) * Prothrombin Time (PT)-International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) \< 1.5 x upper limit of normal * Serum creatinine \< 1.5 x upper limit of normal * Calculated creatinine clearance of \>/= 50 mL/min
Exclusion criteria
* NSCLC patients with predominantly squamous cell carcinoma histology Excluded medical conditions: * History of cardiac disease: Congestive heart failure, Active coronary artery disease (CAD), Cardiac arrhythmias (\>Grade 2 NCI-CTCAE \[National Cancer Institute-Common Terminology Criteria for Adverse Events\] vers. 3.0) * Uncontrolled hypertension despite two anti-hypertensive medications * History of Human immunodeficiency virus (HIV) infection or chronic hepatitis B or C * History of organ allograft * Active clinically serious infections (\> grade 2 NCI-CTCAE vers. 3.0) * Patients with seizure disorder requiring medication * Patients with evidence or history of bleeding diathesis or coagulopathy * Patients undergoing renal dialysis * Pulmonary hemorrhage/ bleeding event \>/= CTCAE grade 2 within four weeks prior to the first dose of the study drug * Any other hemorrhage/ bleeding event \>/= CTCAE grade 3 within four weeks prior to the first dose of the study drug * Thrombotic or embolic venous or arterial events such as cerebrovascular accident * Pregnant or breast-feeding women. * Any condition which could affect the absorption or pharmacokinetics of the study drug * Prior treatment with other Vascular Endothelial Growth Factor (VEGF) (R) inhibitors, including compounds that impact vascularity (i.e. sunitinib, thalidomide, vandetanib, vascular disrupting agents \[VDA\], VEGF-trap and other experimental agents of this class). Only bevacizumab (Avastin) is permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization of the first subject until 36 months later | Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. Overall survival of subjects alive at the time of analysis will be censored at their last date of follow-up or database cut off date whichever came first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control | From randomization of the first subject until 36 months later assessed every 6 weeks | Disease control (DC) was defined as the proportion of patients whose best response was Complete Response \[CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)\] or Partial Response \[PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD\] or Stable Disease \[SD: steady state of disease which was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD)\]. |
| Objective Tumor Response | From randomization of the first subject until 36 months later assessed every 6 weeks | Objective tumor response was defined as the proportion of patients whose best response was Complete Response \[CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)\] or Partial Response \[PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD\] over the whole duration of study. |
| Time to Progression | From randomization of the first subject until 36 months later assessed every 6 weeks | Time to progression (TTP) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier). |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) | The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The 'Global Health status' subscale consists of question 15 of the questionnaire. The score of 'Global Health status' ranges from 0 (very poor) to 100 (excellent). The change of score ranges from -100 (maximum degree of worsening) to 100 (maximum degree of improvement). |
| Progression-free Survival | From randomization of the first subject until 36 months later assessed every 6 weeks | Progression-free survival (PFS) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute progressive disease. In exceptional circumstances unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression. |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) | A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The dyspnea subscale uses questions 3, 4 and 5 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems). |
| Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) | The Euro-Qol 5D (EQ-5D) is a validated assessment tool of Health Related Quality of Life (HRQOL) and utilities consisting of 15 statements. Patients select those statements that best describe their current health state regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression which is converted into a utility value. Range of scale is from -0.594 (worst possible health state) to 1 (perfect health) based on UK weights. The change of score ranges from -1.594 (high degree of worsening) to 1.594 (high degree of improvement). |
| Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) | A visual analogue scale (EQ VAS) used by patients to rate their current health state from 100 (best imaginable health state) to 0 (worst imaginable health state). The change of score ranges from -100 (high degree of worsening) to 100 (high degree of improvement) |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) | A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The coughing subscale uses question 1 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems). |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Israel, Italy, Japan, Netherlands, Pakistan, Peru, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | 350 |
| Placebo Participants received 2 tablets of placebo orally twice daily (BID) | 353 |
| Total | 703 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Survival Follow up | Consent Withdrawn | 7 | 8 |
| Survival Follow up | Death | 244 | 271 |
| Survival Follow up | Lost to Follow-up | 2 | 1 |
| Treatment | Adverse Event | 41 | 16 |
| Treatment | Consent withdrawn | 15 | 14 |
| Treatment | Lost to Follow-up | 1 | 0 |
| Treatment | non-compliant with study medication | 4 | 0 |
| Treatment | Not treated | 4 | 2 |
| Treatment | Other | 1 | 0 |
| Treatment | Protocol Violation | 5 | 3 |
Baseline characteristics
| Characteristic | Sorafenib (Nexavar, BAY43-9006) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.9 Years STANDARD_DEVIATION 10.7 | 60.9 Years STANDARD_DEVIATION 9.8 | 59.9 Years STANDARD_DEVIATION 10.3 |
| Age, Customized >= 65 and < 75 years | 91 Participants | 102 Participants | 193 Participants |
| Age, Customized < 65 years | 239 Participants | 222 Participants | 461 Participants |
| Age, Customized >= 75 years | 20 Participants | 29 Participants | 49 Participants |
| Brain metastasis Missing | 1 Participants | 0 Participants | 1 Participants |
| Brain metastasis No | 293 Participants | 299 Participants | 592 Participants |
| Brain metastasis Yes | 56 Participants | 54 Participants | 110 Participants |
| ECOG (Eastern Cooperative Oncology Group) performance status 0 | 110 Participants | 110 Participants | 220 Participants |
| ECOG (Eastern Cooperative Oncology Group) performance status 1 | 233 Participants | 242 Participants | 475 Participants |
| ECOG (Eastern Cooperative Oncology Group) performance status 2 | 1 Participants | 0 Participants | 1 Participants |
| ECOG (Eastern Cooperative Oncology Group) performance status Missing | 6 Participants | 1 Participants | 7 Participants |
| Number of participants with prior anti-cancer therapy and diagnostic procedures 2 regimens | 188 Participants | 197 Participants | 385 Participants |
| Number of participants with prior anti-cancer therapy and diagnostic procedures 3 regimens | 158 Participants | 153 Participants | 311 Participants |
| Number of participants with prior anti-cancer therapy and diagnostic procedures 4 regimens | 3 Participants | 3 Participants | 6 Participants |
| Number of participants with prior anti-cancer therapy and diagnostic procedures 5 regimens | 1 Participants | 0 Participants | 1 Participants |
| Prior EGFR (Epidermal Growth Factor Receptor) inhibitor treatment No | 141 Participants | 146 Participants | 287 Participants |
| Prior EGFR (Epidermal Growth Factor Receptor) inhibitor treatment Yes | 209 Participants | 207 Participants | 416 Participants |
| Region (CRF [case report form]) Group 1 (North America, Northern/Western Europe) | 122 Participants | 119 Participants | 241 Participants |
| Region (CRF [case report form]) Group 2 (S. America, Eastern Europe, Asia-Pacific) | 228 Participants | 234 Participants | 462 Participants |
| Sex: Female, Male Female | 164 Participants | 144 Participants | 308 Participants |
| Sex: Female, Male Male | 186 Participants | 209 Participants | 395 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 332 / 346 | 289 / 351 |
| serious Total, serious adverse events | 136 / 346 | 111 / 351 |
Outcome results
Primary
Overall Survival
Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. Overall survival of subjects alive at the time of analysis will be censored at their last date of follow-up or database cut off date whichever came first.
Time frame: From randomization of the first subject until 36 months later
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Overall Survival | 248 Days |
| Placebo | Overall Survival | 253 Days |
Comparison: Test for superiority of Sorafenib over Placebop-value: 0.468795% CI: [0.8409, 1.1735]Log Rank
Secondary
Disease Control
Disease control (DC) was defined as the proportion of patients whose best response was Complete Response \[CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)\] or Partial Response \[PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD\] or Stable Disease \[SD: steady state of disease which was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD)\].
Time frame: From randomization of the first subject until 36 months later assessed every 6 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Disease Control | 0.4714 Proportion of participants |
| Placebo | Disease Control | 0.2465 Proportion of participants |
p-value: <0.00000195% CI: [0.1575, 0.2952]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status
The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The 'Global Health status' subscale consists of question 15 of the questionnaire. The score of 'Global Health status' ranges from 0 (very poor) to 100 (excellent). The change of score ranges from -100 (maximum degree of worsening) to 100 (maximum degree of improvement).
Time frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Population: Patient report outcomes (PRO) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 2 (n=295, 309) | -6.158 Scores on a scale | Standard Deviation 22.435 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 3 (n=233, 188) | -5.222 Scores on a scale | Standard Deviation 19.881 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 4 (n= 187, 119) | -2.763 Scores on a scale | Standard Deviation 19.7 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 5 (n= 158, 92) | -3.586 Scores on a scale | Standard Deviation 18.843 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 6 (n=136, 60) | -5.270 Scores on a scale | Standard Deviation 19.845 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | End of treatment (up to Cycle 41, n=192, 221) | -12.153 Scores on a scale | Standard Deviation 24.535 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 6 (n=136, 60) | -3.056 Scores on a scale | Standard Deviation 16.089 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 2 (n=295, 309) | -3.398 Scores on a scale | Standard Deviation 18.37 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 5 (n= 158, 92) | -3.080 Scores on a scale | Standard Deviation 18.806 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 3 (n=233, 188) | -2.305 Scores on a scale | Standard Deviation 18.976 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | End of treatment (up to Cycle 41, n=192, 221) | -12.142 Scores on a scale | Standard Deviation 21.78 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status | Cycle 4 (n= 187, 119) | -3.782 Scores on a scale | Standard Deviation 16.728 |
p-value: 0.3121Mixed Models Analysis
Secondary
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale
A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The coughing subscale uses question 1 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems).
Time frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Population: Patient report outcomes (PRO) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 2 (n=297, 314 | 0.786 Scores on a scale | Standard Deviation 25.91 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 3 (n=234, 192) | -1.567 Scores on a scale | Standard Deviation 24.753 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 4 (n=187, 121) | -2.674 Scores on a scale | Standard Deviation 26.751 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 5 (n=154, 92) | -0.216 Scores on a scale | Standard Deviation 25.422 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 6 (n=134, 61) | -2.239 Scores on a scale | Standard Deviation 23.904 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | End of treatment (up to Cycle 41) (n=194, 225) | 8.763 Scores on a scale | Standard Deviation 27.103 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 6 (n=134, 61) | -3.825 Scores on a scale | Standard Deviation 29.875 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 2 (n=297, 314 | 2.866 Scores on a scale | Standard Deviation 24.325 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 5 (n=154, 92) | -1.812 Scores on a scale | Standard Deviation 24.392 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 3 (n=234, 192) | -0.174 Scores on a scale | Standard Deviation 23.754 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | End of treatment (up to Cycle 41) (n=194, 225) | 5.333 Scores on a scale | Standard Deviation 29.734 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale | Cycle 4 (n=187, 121) | 0.000 Scores on a scale | Standard Deviation 26.527 |
p-value: 0.2948Mixed Models Analysis
Secondary
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea
A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The dyspnea subscale uses questions 3, 4 and 5 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems).
Time frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Population: Patient report outcomes (PRO) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 2 (n=290, 309) | 3.678 Scores on a scale | Standard Deviation 16.251 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 3 (n=232, 189) | 0.958 Scores on a scale | Standard Deviation 16.021 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 4 (n=186, 120) | 3.226 Scores on a scale | Standard Deviation 17.258 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 5 (n=153, 91) | 3.486 Scores on a scale | Standard Deviation 17.169 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 6 (n=133, 61) | 2.840 Scores on a scale | Standard Deviation 16.843 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | End of treatment (up to Cycle 31, n=191, 222) | 12.158 Scores on a scale | Standard Deviation 21.694 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 6 (n=133, 61) | 2.004 Scores on a scale | Standard Deviation 14.7 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 2 (n=290, 309) | 3.740 Scores on a scale | Standard Deviation 17.806 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 5 (n=153, 91) | 3.419 Scores on a scale | Standard Deviation 17.739 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 3 (n=232, 189) | 2.058 Scores on a scale | Standard Deviation 17.984 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | End of treatment (up to Cycle 31, n=191, 222) | 10.611 Scores on a scale | Standard Deviation 22.738 |
| Placebo | Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea | Cycle 4 (n=186, 120) | 2.963 Scores on a scale | Standard Deviation 16.343 |
p-value: 0.8344Mixed Models Analysis
Secondary
Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score
The Euro-Qol 5D (EQ-5D) is a validated assessment tool of Health Related Quality of Life (HRQOL) and utilities consisting of 15 statements. Patients select those statements that best describe their current health state regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression which is converted into a utility value. Range of scale is from -0.594 (worst possible health state) to 1 (perfect health) based on UK weights. The change of score ranges from -1.594 (high degree of worsening) to 1.594 (high degree of improvement).
Time frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Population: Patient report outcomes (PRO) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | Cycle 3 (n=228, 186) | -0.0627 Scores on a scale | Standard Deviation 0.2402 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | Cycle 5 (n=150, 91) | -0.0439 Scores on a scale | Standard Deviation 0.2022 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | End of treatment (up to cycle 41) (n=188, 219) | -0.1845 Scores on a scale | Standard Deviation 0.3348 |
| Placebo | Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | Cycle 3 (n=228, 186) | -0.0386 Scores on a scale | Standard Deviation 0.1998 |
| Placebo | Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | Cycle 5 (n=150, 91) | -0.0728 Scores on a scale | Standard Deviation 0.2373 |
| Placebo | Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score | End of treatment (up to cycle 41) (n=188, 219) | -0.1442 Scores on a scale | Standard Deviation 0.3108 |
p-value: 0.1438Mixed Models Analysis
Secondary
Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score
A visual analogue scale (EQ VAS) used by patients to rate their current health state from 100 (best imaginable health state) to 0 (worst imaginable health state). The change of score ranges from -100 (high degree of worsening) to 100 (high degree of improvement)
Time frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Population: Patient report outcomes (PRO) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | Cycle 3 (n=218 , 183) | -3.73 Scores on a scale | Standard Deviation 16.53 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | Cycle 5 (n=144, 89) | -5.39 Scores on a scale | Standard Deviation 16.66 |
| Sorafenib (Nexavar, BAY43-9006) | Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | End of treatment (up to Cycle 41, n=184, 216) | -12.72 Scores on a scale | Standard Deviation 16.65 |
| Placebo | Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | Cycle 3 (n=218 , 183) | -3.48 Scores on a scale | Standard Deviation 17.35 |
| Placebo | Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | Cycle 5 (n=144, 89) | -2.48 Scores on a scale | Standard Deviation 16.37 |
| Placebo | Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score | End of treatment (up to Cycle 41, n=184, 216) | -10.75 Scores on a scale | Standard Deviation 18.9 |
p-value: 0.9228Mixed Models Analysis
Secondary
Objective Tumor Response
Objective tumor response was defined as the proportion of patients whose best response was Complete Response \[CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)\] or Partial Response \[PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD\] over the whole duration of study.
Time frame: From randomization of the first subject until 36 months later assessed every 6 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Objective Tumor Response | 0.0486 Proportion of participants |
| Placebo | Objective Tumor Response | 0.0085 Proportion of participants |
p-value: 0.00087695% CI: [0.0137, 0.0642]Cochran-Mantel-Haenszel
Secondary
Progression-free Survival
Progression-free survival (PFS) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute progressive disease. In exceptional circumstances unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression.
Time frame: From randomization of the first subject until 36 months later assessed every 6 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Progression-free Survival | 84 Days |
| Placebo | Progression-free Survival | 43 Days |
Comparison: Test for superiority of Sorafenib over Placebop-value: <0.000195% CI: [0.5139, 0.7165]Log Rank
Secondary
Time to Progression
Time to progression (TTP) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier).
Time frame: From randomization of the first subject until 36 months later assessed every 6 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Time to Progression | 89 Days |
| Placebo | Time to Progression | 43 Days |
Comparison: Test for superiority of Sorafenib over Placebop-value: <0.000195% CI: [0.4526, 0.6492]Log Rank