A Study To Describe The Real World Use Of Bosutinib In The UK And Netherlands

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02546375
• Collaborator: pH Associates (Other)
• Enrollment: 87
• Locations: 3
• Actual Duration (Months): 18.1
• Patients Per Site: 29
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The purpose of this study is to describe the efficacy and safety of bosutinib in patients with chronic myeloid leukaemia used in a real world setting

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukaemia	Drug: Bosutinib

Study Design

• Study Type: Observational
• Actual Enrollment: 87 participants
• Observational Model: Case-Only
• Time Perspective: Retrospective
• Official Title: A RETROSPECTIVE OBSERVATIONAL RESEARCH STUDY TO DESCRIBE THE REAL WORLD USE OF BOSUTINIB IN THE UK AND NETHERLANDS
• Actual Study Start Date: Jul 15, 2015
• Actual Primary Completion Date: Jan 16, 2017
• Actual Study Completion Date: Jan 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Chronic Myeloid Leukaemia Patients diagnosed with chronic myeloid leukaemia treated with Bosutinib	Drug: Bosutinib; Bosutinib 100mg film-coated tablets; Bosutinib 500mg film-coated tablets Dosage as prescribed at treating institution; (observational study); Other Names: Bosulif

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Cumulative Complete Haematological Response (CHR) [Baseline up to 5.5 years]

   Haematological response used blood sample of the participants to evaluate response to treatment for CML. Based on the European LeukemiaNet (ELN) 2013 definition: CHR is defined as platelet count less than (<) 450*10^9 per liter, white blood cells count <10*10^9 per liter, no immature granulocytes and <5 percent (%) basophils on differential and a non-palpable spleen.

2. Percentage of Participants With Cumulative Partial Haematological Response (PHR) [Baseline up to 5.5 years]

   Haematological response used blood sample of the participants to evaluate response to treatment for CML.

3. Percentage of Participants With Cumulative Complete Cytogenetic Response (CCyR) [Baseline up to 5.5 years]

   Cytogenetic response (CyR) used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by chromosome banding analysis (CBA) or fluorescence in situ hybridisation (FISH). CCyR was indicated by absence of Philadelphia chromosome positive (Ph+) cells metaphases from FISH of blood interphase cell nuclei.

4. Percentage of Participants With Cumulative Minor Cytogenetic Response (MCyR) [Baseline up to 5.5 years]

   CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. MCyR was indicated by presence of 36-65% Ph+ cells from CBA of bone marrow metaphases.

5. Percentage of Participants With Cumulative Minimal Cytogenetic Response (mCyR) [Baseline up to 5.5 years]

   CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. mCyR was indicated by presence of 66-95% Ph+ cells from CBA of bone marrow metaphases.

6. Percentage of Participants With Cumulative Partial Cytogenetic Response (PCyR) [Baseline up to 5.5 years]

   CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. PCyR was indicated by presence of 1-35% Ph+ cells from CBA of bone marrow metaphases.

7. Percentage of Participants With Cumulative Complete Molecular Response 4.0 (MR4.0) [Baseline up to 5.5 years]

   Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.0 was defined and recorded as detectable disease with <0.01% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with greater than (>) 10,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.

8. Percentage of Participants With Cumulative Complete Molecular Response 4.5 (MR4.5) [Baseline up to 5.5 years]

   Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.5 was defined and recorded as detectable disease with <0.0032% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with >32,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.

9. Percentage of Participants With Cumulative Major Molecular Response (MMR)/Molecular Response 3.0 (MR3.0) [Baseline up to 5.5 years]

   Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MMR was defined as a BCR-ABL1 to ABL1 less than or equal to (<=) 0.1% on the IS.

Secondary Outcome Measures

1. Percentage of Participants With Treatment Related Adverse Events (AEs) [Baseline up to 5.5 years]

   Treatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. Relatedness to Bosutinib was assessed by the investigator.

2. Percentage of Participants With Treatment Related Adverse Events (AEs) Greater Than or Equal to Grade 3 [Baseline up to 5.5 years]

   Treatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.

3. Progression-free Survival (PFS) [Year 1, 2, 3]

   PFS was defined as the duration between initiation of Bosutinib therapy and date of progression estimated by the treating physician or death of participant (all causes combined). Progression was defined as change from chronic phase of CML (CP-CML) to accelerated phase of CML (AP-CML) or to blast crisis of CML (BC-CML). CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy. Participants who were alive at the date of last assessment were censored on the date of data collection.

4. Overall Survival (OS) [From baseline up to 1 Year, baseline up to Year 2, baseline up to Year 3]

   OS was defined as the duration from initiation of Bosutinib therapy to date of death (all causes combined). For participants who were alive or lost to follow-up (LTFU), overall survival was censored on the date of data collection or date LTFU, respectively.

5. Percentage of Participants With Disease Progression [Year 1, 2, 3]

   Progression was defined as change from CP-CML to AP-CML or to BC-CML. CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy.

6. Percentage of Participants With Permanent Discontinuation From Bosutinib Therapy [Baseline up to 5.5 years]

7. Cross-Intolerance Between Bosutinib and Previous Therapy [Baseline up to 5.5 years]

   Cross-intolerance was defined as percentage of participants who permanently discontinued bosutinib due to an adverse event which also resulted in discontinuation of a previous treatment (imatinib, dasatinib, nilotinib).

8. Mean Dose of Bosutinib at Initiation of Treatment [Baseline up to 5.5 years]

9. Relative Bosutinib Dose Intensity [Baseline up to 5.5 years]

   Relative dose intensity was defined as the percentage of daily dose received over the expected daily dose of the study drug.

10. Duration of Bosutinib Therapy [Baseline up to 5.5 years]

    The duration from initiation of Bosutinib therapy up to the end of Bosutinib therapy was reported in this outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Ph+ CML aged ≥18 years at bosutinib initiation.

• Prescribed bosutinib (irrespective of the phase of their disease) EITHER in normal clinical practice since it received marketing authorisation (27th March 2013) by the EMA11 OR via the compassionate use programme prior to marketing authorization.

• Where required, evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• Prescribed bosutinib as part of an interventional clinical trial programme.

• Initiated on bosutinib less than 3 months prior to data collection taking place.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Liverpool Hospital	Liverpool	Merseyside	United Kingdom	L7 8XP
2	Hammersmith Hospital	London		United Kingdom	W12 0HS
3	Nottingham University Hospital	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• Pfizer
• pH Associates

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02546375
• Other Study ID Numbers: B1871052
• First Posted: Sep 10, 2015
• Last Update Posted: Jul 15, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Pfizer: Bosutinib; chronic myeloid leukaemia; retrospective; observational
• Additional relevant MeSH terms: Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

Participant Flow

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive chronic myeloid leukemia (CML) receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 milligram (mg), were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved Summary of Product Characteristics (SmPC).
Period Title: Overall Study
STARTED	87
COMPLETED	87
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Overall Participants	87
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.3 (14.3)
Sex/Gender, Customized (Count of Participants)
Female	40 46%
Male	47 54%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Cumulative Complete Haematological Response (CHR)
Description	Haematological response used blood sample of the participants to evaluate response to treatment for CML. Based on the European LeukemiaNet (ELN) 2013 definition: CHR is defined as platelet count less than (<) 450*10^9 per liter, white blood cells count <10*10^9 per liter, no immature granulocytes and <5 percent (%) basophils on differential and a non-palpable spleen.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	93 106.9%

2. Primary Outcome

Title	Percentage of Participants With Cumulative Partial Haematological Response (PHR)
Description	Haematological response used blood sample of the participants to evaluate response to treatment for CML.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	94 108%

3. Primary Outcome

Title	Percentage of Participants With Cumulative Complete Cytogenetic Response (CCyR)
Description	Cytogenetic response (CyR) used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by chromosome banding analysis (CBA) or fluorescence in situ hybridisation (FISH). CCyR was indicated by absence of Philadelphia chromosome positive (Ph+) cells metaphases from FISH of blood interphase cell nuclei.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	67 77%

4. Primary Outcome

Title	Percentage of Participants With Cumulative Minor Cytogenetic Response (MCyR)
Description	CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. MCyR was indicated by presence of 36-65% Ph+ cells from CBA of bone marrow metaphases.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	77 88.5%

5. Primary Outcome

Title	Percentage of Participants With Cumulative Minimal Cytogenetic Response (mCyR)
Description	CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. mCyR was indicated by presence of 66-95% Ph+ cells from CBA of bone marrow metaphases.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	80 92%

6. Primary Outcome

Title	Percentage of Participants With Cumulative Partial Cytogenetic Response (PCyR)
Description	CyR used bone marrow/blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: CyR was measured by CBA or FISH. PCyR was indicated by presence of 1-35% Ph+ cells from CBA of bone marrow metaphases.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	77 88.5%

7. Primary Outcome

Title	Percentage of Participants With Cumulative Complete Molecular Response 4.0 (MR4.0)
Description	Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.0 was defined and recorded as detectable disease with <0.01% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with greater than (>) 10,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	33 37.9%

8. Primary Outcome

Title	Percentage of Participants With Cumulative Complete Molecular Response 4.5 (MR4.5)
Description	Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MR4.5 was defined and recorded as detectable disease with <0.0032% BCR-ABL1 transcripts on IS or undetectable disease in cDNA with >32,000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1 transcripts.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	27 31%

9. Primary Outcome

Title	Percentage of Participants With Cumulative Major Molecular Response (MMR)/Molecular Response 3.0 (MR3.0)
Description	Molecular response used blood sample of the participants to evaluate response to treatment for CML. Based on the ELN 2013 definition: Molecular response used breakpoint cluster region/Abelson (BCR-ABL1) transcript measured by real time quantitative polymerase chain reaction (RT-Q-PCR). Evaluation was expressed as percentage of ratio of BCR-ABL1 transcripts to ABL1 transcripts according to the international scale (IS) or the ratio of BCR/ABL1 transcripts to other internationally recognized control transcripts levels. MMR was defined as a BCR-ABL1 to ABL1 less than or equal to (<=) 0.1% on the IS.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
Number [percentage of participants]	55 63.2%

10. Secondary Outcome

Title	Percentage of Participants With Treatment Related Adverse Events (AEs)
Description	Treatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. Relatedness to Bosutinib was assessed by the investigator.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Number [percentage of participants]	94 108%

11. Secondary Outcome

Title	Percentage of Participants With Treatment Related Adverse Events (AEs) Greater Than or Equal to Grade 3
Description	Treatment-related AE was any untoward medical occurrence attributed to Bosutinib in a participant who received Bosutinib. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Number [percentage of participants]	21 24.1%

12. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS was defined as the duration between initiation of Bosutinib therapy and date of progression estimated by the treating physician or death of participant (all causes combined). Progression was defined as change from chronic phase of CML (CP-CML) to accelerated phase of CML (AP-CML) or to blast crisis of CML (BC-CML). CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy. Participants who were alive at the date of last assessment were censored on the date of data collection.
Time Frame	Year 1, 2, 3

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Median (95% Confidence Interval) [years]	NA

13. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the duration from initiation of Bosutinib therapy to date of death (all causes combined). For participants who were alive or lost to follow-up (LTFU), overall survival was censored on the date of data collection or date LTFU, respectively.
Time Frame	From baseline up to 1 Year, baseline up to Year 2, baseline up to Year 3

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Median (95% Confidence Interval) [years]	NA

14. Secondary Outcome

Title	Percentage of Participants With Disease Progression
Description	Progression was defined as change from CP-CML to AP-CML or to BC-CML. CP-CML is frequently asymptomatic and diagnosed with <10% blasts. Based on the ELN 2013 definition: AP-CML was defined by the presence of blast cells between 15-29% or blast cells plus promyelocytes >30%, with blasts <30% in blood or bone marrow, platelet count <100*10^9 or clonal chromosome abnormalities in Ph+ cells. BC-CML was defined as blasts in blood or bone marrow >=30%, extramedullary blast proliferation (excluding spleen), large foci or clusters of blasts in bone marrow biopsy.
Time Frame	Year 1, 2, 3

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib. Here, N signifies those participants who were evaluable for this outcome measure and number analyzed (n) signifies those participants who were evaluable at specified time points only.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	84
1 year	3 3.4%
2 year	3 3.4%
3 year	0 0%

15. Secondary Outcome

Title	Percentage of Participants With Permanent Discontinuation From Bosutinib Therapy
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Adverse event	14 16.1%
Loss of response	5 5.7%
Treatment failure	11 12.6%
Participant request	2 2.3%
Death	2 2.3%
Disease progression	1 1.1%
Other	2 2.3%

16. Secondary Outcome

Title	Cross-Intolerance Between Bosutinib and Previous Therapy
Description	Cross-intolerance was defined as percentage of participants who permanently discontinued bosutinib due to an adverse event which also resulted in discontinuation of a previous treatment (imatinib, dasatinib, nilotinib).
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Number [percentage of participants]	1.1 1.3%

17. Secondary Outcome

Title	Mean Dose of Bosutinib at Initiation of Treatment
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Mean (Standard Deviation) [milligram per day]	331.0 (126.6)

18. Secondary Outcome

Title	Relative Bosutinib Dose Intensity
Description	Relative dose intensity was defined as the percentage of daily dose received over the expected daily dose of the study drug.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Number [percentage of daily dose]	66

19. Secondary Outcome

Title	Duration of Bosutinib Therapy
Description	The duration from initiation of Bosutinib therapy up to the end of Bosutinib therapy was reported in this outcome measure.
Time Frame	Baseline up to 5.5 years

Outcome Measure Data

Analysis Population Description

All enrolled participants with Philadephia chromosome positive CML in chronic phase received at least 1 dose of Bosutinib.

Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
Measure Participants	87
Median (Full Range) [months]	15.6

Adverse Events

Time Frame	Baseline up to 5.5 years
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Arm/Group Title	Bosutinib
Arm/Group Description	Participants with Philadelphia chromosome-positive CML receiving imatinib, dasatinib or nilotinib prior to enrollment in the study, who were treated with single daily oral dose of Bosutinib 100 to 500 mg, were observed up to a maximum duration of 5.5 years. Dosage and use of Bosutinib was based on treating physician, according to approved SmPC.
All Cause Mortality
	Bosutinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bosutinib
	Affected / at Risk (%)	# Events
Total	17/87 (19.5%)
Blood and lymphatic system disorders
Anaemia	0/87 (0%)
Creatinine increased	0/87 (0%)
Neutropenia	0/87 (0%)
Thrombocytopenia	1/87 (1.1%)
Cardiac disorders
Atrial fibrillation	0/87 (0%)
Cardiac failure	2/87 (2.3%)
Hypertension	0/87 (0%)
Eye disorders
Diseases of the eye	1/87 (1.1%)
Gastrointestinal disorders
Abdominal Distension	0/87 (0%)
Abdominal pain	0/87 (0%)
Constipation	0/87 (0%)
Diarrhoea	1/87 (1.1%)
Dyspepsia	0/87 (0%)
Nausea	0/87 (0%)
Vomiting	1/87 (1.1%)
General disorders
Alopecia	0/87 (0%)
Asthenia	0/87 (0%)
Chest pain	1/87 (1.1%)
Fatigue	0/87 (0%)
Oedema	0/87 (0%)
Pain	0/87 (0%)
Pyrexia	0/87 (0%)
Other	1/87 (1.1%)
Lack of efficacy	4/87 (4.6%)
Haematological - not determined	1/87 (1.1%)
Hepatobiliary disorders
Alanine aminotransferase increased	1/87 (1.1%)
Hepatotoxicity	0/87 (0%)
Infections and infestations
Pneumonia	1/87 (1.1%)
Respiratory tract infection	0/87 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/87 (0%)
Bone pain	0/87 (0%)
Muscle cramps	0/87 (0%)
Myalgia	0/87 (0%)
Pain in extremity	0/87 (0%)
Nervous system disorders
Dizziness	0/87 (0%)
Headache	0/87 (0%)
Renal and urinary disorders
Pyelonephritis	1/87 (1.1%)
Reproductive system and breast disorders
Pregnancy	1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	0/87 (0%)
Dyspnoea	0/87 (0%)
Pleural effusion	1/87 (1.1%)
Skin and subcutaneous tissue disorders
Acne	0/87 (0%)
Dry skin	0/87 (0%)
Rash	0/87 (0%)
Other (Not Including Serious) Adverse Events
	Bosutinib
	Affected / at Risk (%)	# Events
Total	81/87 (93.1%)
Blood and lymphatic system disorders
Anaemia	3/87 (3.4%)
Creatinine increased	5/87 (5.7%)
Neutropenia	1/87 (1.1%)
Thrombocytopenia	6/87 (6.9%)
Cardiac disorders
Atrial fibrillation	3/87 (3.4%)
Cardiac failure	0/87 (0%)
Hypertension	1/87 (1.1%)
Cardiac disorder	1/87 (1.1%)
Eye disorders
Diseases of the eye	1/87 (1.1%)
Gastrointestinal disorders
Abdominal Distension	1/87 (1.1%)
Abdominal pain	8/87 (9.2%)
Constipation	1/87 (1.1%)
Diarrhoea	45/87 (51.7%)
Dyspepsia	4/87 (4.6%)
Nausea	18/87 (20.7%)
Vomiting	4/87 (4.6%)
Mucositis	1/87 (1.1%)
Unusual taste in mouth	1/87 (1.1%)
General disorders
Alopecia	3/87 (3.4%)
Asthenia	1/87 (1.1%)
Chest pain	7/87 (8%)
Fatigue	16/87 (18.4%)
Oedema	1/87 (1.1%)
Pain	5/87 (5.7%)
Pyrexia	1/87 (1.1%)
Other	0/87 (0%)
Lack of efficacy	10/87 (11.5%)
Haematological - not determined	4/87 (4.6%)
Fever	1/87 (1.1%)
Medication error	1/87 (1.1%)
Rigors associates with extreme tiredness and thirst	1/87 (1.1%)
	1/87 (1.1%)
Weight gain	1/87 (1.1%)
Hepatobiliary disorders
Alanine aminotransferase increased	15/87 (17.2%)
Hepatotoxicity	1/87 (1.1%)
Infections and infestations
Pneumonia	0/87 (0%)
Respiratory tract infection	1/87 (1.1%)
Flu like symptoms	1/87 (1.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/87 (1.1%)
Bone pain	4/87 (4.6%)
Muscle cramps	1/87 (1.1%)
Myalgia	4/87 (4.6%)
Pain in extremity	6/87 (6.9%)
Vitamin D deficiency	1/87 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Exostosis - benign growths of bone	1/87 (1.1%)
Nervous system disorders
Dizziness	2/87 (2.3%)
Headache	8/87 (9.2%)
Depression	2/87 (2.3%)
Sleep disturbance	1/87 (1.1%)
Renal and urinary disorders
Urinary tract infection	2/87 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/87 (1.1%)
Dyspnoea	3/87 (3.4%)
Pleural effusion	3/87 (3.4%)
Skin and subcutaneous tissue disorders
Acne	1/87 (1.1%)
Dry skin	2/87 (2.3%)
Rash	15/87 (17.2%)
Altered skin sensation	1/87 (1.1%)
Breaking nails	1/87 (1.1%)
Skin lesion	1/87 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.