Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With Breast Cancer

• Progression Free Survival (PFS) Based on Independent Radiologist [ Time Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
  
  

• Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after the last dose ] [ Designated as safety issue: Yes ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
  
  
• Progression Free Survival (PFS) Based on Investigator [ Time Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  Time in weeks from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
  
  
• Percentage of Participants With Objective Response [ Time Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to >=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.
  
  
• Overall Survival (OS) [ Time Frame: Part 2 Baseline until death or up to 24 months ] [ Designated as safety issue: No ]
  Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
  
  
• Duration of Response (DR) [ Time Frame: Part 2 Baseline, every 8 weeks up to 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
  
  
• Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) [ Time Frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and additional concerns on breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures ranges from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL.
  
  
• Euro Quality of Life (EQ-5D)- Health State Profile Utility Score [ Time Frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
  
  
• Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) [ Time Frame: Part 2 Baseline, Week 12, 2 to 6 weeks after last dose ] [ Designated as safety issue: No ]
  EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) = worst imaginable health state to 100 mm =best imaginable health state; higher scores indicate a better health state.
  
  
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29 ] [ Designated as safety issue: No ]
  
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29 ] [ Designated as safety issue: No ]
  
• Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] [ Time Frame: 0 hour (pre-dose) on Day 1, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 29 ] [ Designated as safety issue: No ]
  AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
  
  

This study was terminated on 19 Apr 2010 due to unfavorable risk benefit ratio which did not support continuation in part 2 of the study. Even if the safety profile of the combination of Bosutinib and Exemestane was acceptable 25% of subjects had treatment related liver events including 14% of severe liver events.