BAY43-9006 (Sorafenib) Versus Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma

• Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
  
  

• Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
  
  
• Disease Control (DC) According to Independent Central Review for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
  
  
• Disease Control (DC) According to the Investigator Assessment for the First Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
  
  
• Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
  
  
• Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions:" I have been short in breath" and "I have been coughing"; its score ranges from 0 to 8.
  
  
• Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions:" I have been short in breath" and "I have been coughing"; its score ranges from 0 to 8.
  
  
• Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns.
  
  
• Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns.
  
  
• Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL.
  
  
• Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL.
  
  
• Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
  
  
• Tumor Response According to the Independent Radiological Review for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
  
  
• Tumor Response According to the Investigator Assessment for the First Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes
  
  
• Tumor Response According to the Investigator Assessment for the Second Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes
  
  
• Progression Free Survival According to the Investigator Assessment (Second Intervention Period) [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
  
  
• Overall Survival (OS) [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Overall Survival was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact
  
  
• Slope - Change in Trough Concentration/Cycle [ Time Frame: From start of treatment of the first subject until 15 months later assessed every 4 weeks. ] [ Designated as safety issue: No ]
  Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID (bis in die, twice daily)) to assess any potential trends in trough concentration over time.
  
  
• Average of All Trough Plasma Concentrations [ Time Frame: From start of treatment of the first subject until 15 months later assessed every 4 weeks. ] [ Designated as safety issue: No ]
  Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID).
  
  
• Duration of Response According to the Independent Radiological Review for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact
  
  
• Duration of Response According to the Investigator Assessment for the First Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact
  
  
• Duration of Response According to the Investigator Assessment for the Second Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact
  
  
• Time to Response According to the Independent Radiological Review for the First Intervention Period [ Time Frame: From randomization of the first subject until 15 months later, assessed every 8 weeks ] [ Designated as safety issue: No ]
  Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented
  
  
• Time to Response According to the Investigator Assessment for the First Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks ] [ Designated as safety issue: No ]
  Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented
  
  
• Time to Response According to the Investigator Assessment for the Second Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks ] [ Designated as safety issue: No ]
  Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation) was defined as the time from date of randomization to the earliest date that the response was first documented
  
  
• Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks ] [ Designated as safety issue: No ]
  Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).
  
  
• Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period [ Time Frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks ] [ Designated as safety issue: No ]
  Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).
  
  

Analyses on Biomarkers were exploratory and assessed as tertiary objective of the trial.