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    Clinical Trial Results:
    A Phase 3, Open-Label, Randomized, Parallel, 2-Arm, Multi-Center Study of Talazoparib (BMN 673) Versus Physician’s Choice in Germline BRCA Mutation Subjects With Locally Advanced and/or Metastatic Breast Cancer, Who Have Received Prior Chemotherapy Regimens for Metastatic Disease

    Summary
    EudraCT number
    2013-002716-28
    Trial protocol
    GB   BE   IT   IE   FR   ES   DE   PL  
    Global end of trial date
    05 Mar 2021

    Results information
    Results version number
    v2(current)
    This version publication date
    11 Jan 2022
    First version publication date
    21 Sep 2018
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    673-301
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01945775
    WHO universal trial number (UTN)
    U1111-1155-7579
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Mar 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the progression free survival (PFS) of subjects treated with talazoparib as a monotherapy relative to those treated with protocol-specified physician's choice treatment (PCT).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    14 Oct 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    28 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 27
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Brazil: 25
    Country: Number of subjects enrolled
    France: 50
    Country: Number of subjects enrolled
    Germany: 31
    Country: Number of subjects enrolled
    Ireland: 6
    Country: Number of subjects enrolled
    Israel: 19
    Country: Number of subjects enrolled
    Italy: 11
    Country: Number of subjects enrolled
    Korea, Republic of: 32
    Country: Number of subjects enrolled
    Poland: 11
    Country: Number of subjects enrolled
    Russian Federation: 9
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    Taiwan: 1
    Country: Number of subjects enrolled
    Ukraine: 1
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    United States: 156
    Worldwide total number of subjects
    431
    EEA total number of subjects
    146
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    394
    From 65 to 84 years
    35
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Study was conducted from 14-Oct-2013 to 05-Mar-2021 at multiple sites.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Talazoparib
    Arm description
    Subjects received talazoparib 1 milligram (mg), orally, once daily, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.
    Arm type
    Experimental

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received talazoparib 1 mg, orally, once daily, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 70.2 months).

    Arm title
    Physician's Choice Treatment
    Arm description
    Subjects received 1 of the following drugs in specified regimens, as per the physician’s choice: 1) capecitabine 1250 milligram per meter square (mg/m^2) orally twice daily on Day 1 to 14 in each cycle; 2) eribulin mesylate 1.4 mg/m^2 (equivalent to eribulin 1.23 mg/ m^2), as 2 to 5 minute intravenous (IV) infusion on Day 1 and 8 in each cycle; 3) gemcitabine 1250 mg/m^2 as 30-minute IV infusion on Day 1 and 8 in each cycle; 4) vinorelbine 30 mg/m^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 in each cycle; until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months). One cycle was of 21 days.
    Arm type
    Active comparator

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Capecitabine 1250 milligram per meter square (mg/m^2) orally twice daily on Day 1 to 14 for 21 day cycle, as per the physician’s choice, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months).

    Investigational medicinal product name
    Eribulin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Eribulin mesylate 1.4 mg/m^2 (equivalent to eribulin 1.23 mg/ m^2), as 2 to 5 minute intravenous (IV) infusion on Day 1 and 8 for 21 day cycle, as per the physician’s choice, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months).

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Gemcitabine 1250 mg/m^2 as 30-minute IV infusion on Day 1 and 8 for 21 day cycle, as per the physician’s choice, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months).

    Investigational medicinal product name
    Vinorelbine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Vinorelbine 30 mg/m^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 for 21 day cycle, as per the physician’s choice, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months).

    Number of subjects in period 1
    Talazoparib Physician's Choice Treatment
    Started
    287
    144
    Treated
    286
    126
    Completed
    0
    0
    Not completed
    287
    144
         Consent withdrawn by subject
    11
    21
         Death
    214
    98
         Unspecified
    50
    18
         Lost to follow-up
    12
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Talazoparib
    Reporting group description
    Subjects received talazoparib 1 milligram (mg), orally, once daily, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.

    Reporting group title
    Physician's Choice Treatment
    Reporting group description
    Subjects received 1 of the following drugs in specified regimens, as per the physician’s choice: 1) capecitabine 1250 milligram per meter square (mg/m^2) orally twice daily on Day 1 to 14 in each cycle; 2) eribulin mesylate 1.4 mg/m^2 (equivalent to eribulin 1.23 mg/ m^2), as 2 to 5 minute intravenous (IV) infusion on Day 1 and 8 in each cycle; 3) gemcitabine 1250 mg/m^2 as 30-minute IV infusion on Day 1 and 8 in each cycle; 4) vinorelbine 30 mg/m^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 in each cycle; until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months). One cycle was of 21 days.

    Reporting group values
    Talazoparib Physician's Choice Treatment Total
    Number of subjects
    287 144 431
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    260 134 394
        From 65-84 years
    27 8 35
        85 years and over
    0 2 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    47.5 ( 11.61 ) 49.4 ( 12.12 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    283 141 424
        Male
    4 3 7
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    31 16 47
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    11 1 12
        White
    190 108 298
        More than one race
    0 0 0
        Unknown or Not Reported
    55 19 74
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    31 15 46
        Not Hispanic or Latino
    207 111 318
        Unknown or Not Reported
    49 18 67

    End points

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    End points reporting groups
    Reporting group title
    Talazoparib
    Reporting group description
    Subjects received talazoparib 1 milligram (mg), orally, once daily, until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.

    Reporting group title
    Physician's Choice Treatment
    Reporting group description
    Subjects received 1 of the following drugs in specified regimens, as per the physician’s choice: 1) capecitabine 1250 milligram per meter square (mg/m^2) orally twice daily on Day 1 to 14 in each cycle; 2) eribulin mesylate 1.4 mg/m^2 (equivalent to eribulin 1.23 mg/ m^2), as 2 to 5 minute intravenous (IV) infusion on Day 1 and 8 in each cycle; 3) gemcitabine 1250 mg/m^2 as 30-minute IV infusion on Day 1 and 8 in each cycle; 4) vinorelbine 30 mg/m^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 in each cycle; until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months). One cycle was of 21 days.

    Primary: Progression-Free Survival (PFS): Independent Radiological Facility (IRF) Assessment

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    End point title
    Progression-Free Survival (PFS): Independent Radiological Facility (IRF) Assessment
    End point description
    IRF assessed PFS was defined as time (in months) from randomization until the date of first documented radiologic progressive disease per response evaluation criteria in solid tumors (RECIST) version 1.1 or death from any cause, whichever occurs first. As per RECIST v1.1, progression defined as 1) for target lesions: at least a 20% increase in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), the absolute increase in the sum has to be at least 5 millimetre (mm); 2) for non-target lesions: unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions; 3) and/or appearance of one or more new lesions. The analysis was performed by Kaplan-Meier method. Intent-to-treat (ITT) analysis population included all randomized subjects.
    End point type
    Primary
    End point timeframe
    Baseline until radiologic progressive disease or death due to any cause (up to maximum duration of 36.9 months)
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    287
    144
    Units: months
        median (confidence interval 95%)
    8.6 (7.2 to 9.3)
    5.6 (4.2 to 6.7)
    Statistical analysis title
    Talazoparib versus Physician's Choice Treatment
    Statistical analysis description
    Hazard ratio was based on stratified Cox regression model with treatment as the only covariate (stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system metastasis status).
    Comparison groups
    Talazoparib v Physician's Choice Treatment
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Logrank
    Parameter type
    Log hazard ratio
    Point estimate
    0.542
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.413
         upper limit
    0.711

    Secondary: Percentage of Subjects With Objective Response: Investigator Assessment

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    End point title
    Percentage of Subjects With Objective Response: Investigator Assessment
    End point description
    Investigator assessed overall response was defined as the percentage of subjects with a partial response (PR) or complete response (CR) as defined by RECIST v1.1. For target lesions: 1) CR: disappearance of all non-nodal target lesions. Target lymph nodes must reduce to less than 10 mm in short axis. 2) PR: At least a 30% decrease in the sum of diameters of target lesions, compared to the sum at baseline. For non-target lesions, CR: disappearance of all non-target lesions. ITT analysis population included all randomized subjects. Percentage of subjects with objective response reported are based upon unconfirmed CR/PR. ITT with measurable disease analysis population included all subjects in the ITT population who had at least 1 target lesion identified at baseline.
    End point type
    Secondary
    End point timeframe
    Baseline until radiologic progressive disease or death due to any cause (up to a maximum duration of 36.9 months)
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    219
    114
    Units: percentage of subjects
        number (confidence interval 95%)
    62.6 (55.78 to 68.99)
    27.2 (19.28 to 36.33)
    Statistical analysis title
    Talazoparib versus Physician's Choice Treatment
    Statistical analysis description
    p-value was based on stratified Cochran-Mantel-Haenszel method. Stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system metastasis status.
    Comparison groups
    Talazoparib v Physician's Choice Treatment
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    4.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.93
         upper limit
    8.83

    Secondary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    OS was defined as the time (in months) from randomization to death due to any cause. If death was not observed at the time of study cut-off date or permanently lost to follow-up, OS was censored at the date the subject was last known to be alive on or before the study cut-off date, whichever was earlier. The analysis was performed by Kaplan-Meier method. ITT analysis population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Baseline until death due to any cause or analysis cut-off, up to a maximum duration of 61.4 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    287
    144
    Units: months
        median (confidence interval 95%)
    19.3 (16.6 to 22.5)
    19.5 (17.4 to 22.4)
    Statistical analysis title
    Talazoparib versus Physician's Choice Treatment
    Statistical analysis description
    Hazard ratio was based on stratified Cox regression model with treatment as the only covariate (stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system metastasis status).
    Comparison groups
    Talazoparib v Physician's Choice Treatment
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.1693
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.848
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.67
         upper limit
    1.073

    Secondary: Trough Plasma Talazoparib Concentrations

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    End point title
    Trough Plasma Talazoparib Concentrations [1]
    End point description
    A predose PK sample was considered dose-compliant based on the following criteria: A subject must have received 21 consecutive days of 1 mg talazoparib without dosing interruption prior to sample collection; and the predose PK sample must have been collected 24 hours +/- 10% (2 hours and 24 minutes) after the previous day’s dose and no more than 5 minutes (0.083 hours) after the administration of the dose on the day of PK sample collection. Analysis population included subjects who received at least 1 dose of talazoparib and had dose compliant pharmacokinetic (PK) predose sample. Here, “n" signifies number of subjects who were evaluable for the specified categories. This endpoint was not planned to be analysed for the reporting arm “Physician’s Choice Treatment”.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycle 2, 3 and 4
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was planned to be analyzed only for reporting arm "Talazoparib".
    End point values
    Talazoparib
    Number of subjects analysed
    175
    Units: Picogram per milliliter (pg/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 2 Day 1: Predose (n=137)
    3370 ( 76.9 )
        Cycle 3 Day 1: Predose (n=120)
    3570 ( 49.9 )
        Cycle 4 Day 1: Predose (n=107)
    3400 ( 48.4 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a subject administered study drug or other protocol-imposed intervention, regardless of attribution. 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 primary analysis data cut-off date or the day before initiation of a new antineoplastic therapy or 30 days after the date of the last dose date of study drug, whichever occurred first, that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs. Safety analysis population.
    End point type
    Secondary
    End point timeframe
    Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician’s Choice Treatment: Baseline up to maximum duration of 46.1 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    286
    126
    Units: subjects
        TEAEs
    282
    123
        SAEs
    103
    39
    No statistical analyses for this end point

    Secondary: Number of Subjects With Grade 3 or 4 Post baseline Toxicities in Laboratory Parameters: Hematology

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    End point title
    Number of Subjects With Grade 3 or 4 Post baseline Toxicities in Laboratory Parameters: Hematology
    End point description
    Toxicity grades were evaluated based on as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). NCI CTCAE v4.03 defined the severity grade as: grade 1 (mild), grade 2 (moderate), grade 3 (severe) and grade 4 (potentially life threatening) and grade 5 (death related to AE) for each parameter. Key hematology parameters included hemoglobin (gram per liter [g/L]), leukocytes (10^6 cells per liter), lymphocytes (10^6 cells per liter), neutrophils (10^6 cells per liter), and platelets (10^9 cells per liter). Low value indicated lower values than the baseline values and high value indicated higher values than the baseline values. Only those categories in which at least 1 subject had data were reported. Safety analysis population included all subjects who received at least 1 dose of any study drug (talazoparib or protocol-specified PCT).
    End point type
    Secondary
    End point timeframe
    Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician’s Choice Treatment: Baseline up to maximum duration of 46.1 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    286
    126
    Units: subjects
        Hemoglobin: Low value
    115
    8
        Leukocytes: Low value
    43
    31
        Lymphocytes: Low value
    54
    11
        Neutrophils: Low value
    65
    48
        Platelets: Low value
    44
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Grade 3 or 4 Post baseline Toxicities in Laboratory Parameters: Chemistry

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    End point title
    Number of Subjects With Grade 3 or 4 Post baseline Toxicities in Laboratory Parameters: Chemistry
    End point description
    Toxicity grades were evaluated based on as NCI CTCAE v4.03. NCI CTCAE v4.03 defined the severity grade as: grade 1 (mild), grade 2 (moderate), grade 3 (severe) and grade 4 (potentially life threatening) and grade 5 (death related to AE) for each parameter. Key chemistry parameters included alanine aminotransferase (units per liter), alkaline phosphatase (units per liter), aspartate aminotransferase (units per liter) and bilirubin (micromole per liter). High value indicated higher values than the baseline values and low value indicated lower values than the baseline values. Only those categories in which at least 1 subject had data were reported. Safety analysis population included all subjects who received at least 1 dose of any study drug (talazoparib or protocol-specified PCT).
    End point type
    Secondary
    End point timeframe
    Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician’s Choice Treatment: Baseline up to maximum duration of 46.1 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    286
    126
    Units: subjects
        Alanine Aminotransferase: High Value
    5
    3
        Alkaline Phosphatase: High Value
    6
    2
        Aspartate Aminotransferase: High Value
    7
    4
        Bilirubin: High Value
    4
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Potentially Clinically Significant Changes From Baseline in Vital Signs

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    End point title
    Number of Subjects With Potentially Clinically Significant Changes From Baseline in Vital Signs
    End point description
    Criteria for potentially clinically significant changes in vital signs included a) Systolic blood pressure: 1) absolute results (AB) greater than (>) 180 millimetre of mercury (mmHg) and increase from baseline (IFB) greater than or equal to (>=) 40 mmHg, 2) absolute results less than (<) 90 mmHg and decrease from baseline (DFB) >30 mmHg; b) Diastolic blood pressure: 1) absolute results >110 mmHg and >=30 mmHg increase from baseline, 2) absolute results <50 mmHg and >20 mmHg decrease from baseline 3) >=20 mmHg increase from baseline); c) Heart rate: 1) absolute results>120 beats per minute [bpm] and >30 bpm increase from baseline, 2) absolute results <50 bpm and >20 bpm decrease from baseline) and d) Weight: >10 percent [%] decrease from baseline. Safety analysis population included all subjects who received at least 1 dose of any study drug (talazoparib or protocol-specified PCT).
    End point type
    Secondary
    End point timeframe
    Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician’s Choice Treatment: Baseline up to maximum duration of 46.1 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    286
    126
    Units: subjects
        SBP: AB>180 mmHg and IFB >=40 mmHg
    3
    2
        SBP: AB<90 mmHg and DFB >30 mmHg
    8
    2
        DBP: AB>110 mmHg and IFB >=30 mmHg
    0
    0
        DBP: AB<50 mmHg and DFB>20 mmHg
    15
    7
        DBP: IFB>=20 mmHg
    39
    13
        Heart rate: AB >120 bpm and IFB >30 bpm
    6
    2
        Heart rate: AB <50 bpm and DFB >20 bpm
    2
    0
        Weight: >10% DFB
    23
    13
    No statistical analyses for this end point

    Secondary: Number of Subjects Taking At least One Concomitant Medication

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    End point title
    Number of Subjects Taking At least One Concomitant Medication
    End point description
    Any medication (other than study drug) which was administered to subjects during study after first dose of study drug were considered as concomitant medications. Safety analysis population included all subjects who received at least 1 dose of any study drug (talazoparib or protocol-specified PCT).
    End point type
    Secondary
    End point timeframe
    Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician’s Choice Treatment: Baseline up to maximum duration of 46.1 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    286
    126
    Units: subjects
    281
    126
    No statistical analyses for this end point

    Other pre-specified: Duration of Response (DOR): Investigator Assessment

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    End point title
    Duration of Response (DOR): Investigator Assessment
    End point description
    DOR = time from first radiographic documentation of OR (PR or CR) till radiographic disease progression (PD) as per RECIST v1.1 by investigator assessment or to death due to any cause, whichever was first. RECIST 1.1, a) target lesion (TL): CR= disappearance of all non-nodal TL, target lymph nodes reduce to <10 mm in short axis, PR= at least 30% decrease in sum of diameters of TL, compared to the sum at baseline, PD= at least 20% increase in sum of TL measurements, compared to smallest sum on study including baseline, absolute increase in sum has to be at least 5 mm; b) for non-TL: CR= disappearance of all non-TL. PD= unequivocal progression of non-TL, such that treatment has failed, disease is progressing, regardless of status of TL; c) PD = and/or appearance of >=1 new lesions. Kaplan-Meier method used. ITT with measurable disease analysis population: ITT population who had at least 1 target lesion identified at baseline.
    End point type
    Other pre-specified
    End point timeframe
    From first documentation of CR or PR until disease progression or death due to any cause, whichever occurred first (up to 36.9 months)
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    219
    114
    Units: months
        median (inter-quartile range (Q1-Q3))
    5.4 (2.8 to 11.2)
    3.1 (2.4 to 6.7)
    No statistical analyses for this end point

    Other pre-specified: Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at Average Duration Over Week 4 up to Week 160

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    End point title
    Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at Average Duration Over Week 4 up to Week 160
    End point description
    EORTC QLQ-C30: 30 questions to assess subject QoL. First 28 questions:5 functional scales(physical, role,cognitive,emotional,social),3 symptom scales(fatigue,nausea and vomiting,pain) and other single items(dyspnea,appetite loss,insomnia,constipation,diarrhea and financial difficulties).Each question assessed on 4-point scale(1=not at all, 2=a little, 3=quite a bit, 4=very much);functional scale:higher score=better level of functioning; symptom scale: higher score=more severe symptoms. Last 2 questions: GHS/QoL. Each question assessed on 7-point scale 1(very poor)-7(excellent). Score averaged, transformed to 0-100 scale; higher score=better QoL. Patient-reported outcomes (PRO) evaluable population: all subjects who completed PRO questionnaire at baseline and atleast 1 visit postbaseline.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 4 up to Week 160
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    262
    114
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    3.0 (1.2 to 4.8)
    -5.4 (-8.8 to -2.0)
    Statistical analysis title
    Talazoparib versus Physician's Choice Treatment
    Statistical analysis description
    Analysis was based on repeated measures mixed-effect model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate. Analysis was based on restricted maximum likelihood using unstructured covariance matrix.
    Comparison groups
    Talazoparib v Physician's Choice Treatment
    Number of subjects included in analysis
    376
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    8.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.6
         upper limit
    12.3

    Other pre-specified: Time to Deterioration (TTD) in Global Health Status (GHS)/Quality of Life (QOL)

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    End point title
    Time to Deterioration (TTD) in Global Health Status (GHS)/Quality of Life (QOL)
    End point description
    TTD in global health status (GHS)/QoL=time (in months) from randomization to the first observation with >=10 point decrease and no subsequent observations with<10 point decrease from baseline in GHS/QoL score based on EORTC-QLQ-C30. EORTC QLQ-C30 is a cancer-specific instrument with 30 questions to assess subject quality of life. Question 29 and 30 were used to evaluate GHS/QoL. Each question was assessed on a 7-point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning. Here, 99999 = upper 95% CI was not estimable, since only few subjects had event. PRO-evaluable population included all subject who completed the PRO questionnaire at baseline and at least 1 visit postbaseline.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to a maximum duration of 36.9 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    262
    114
    Units: months
        median (confidence interval 95%)
    24.3 (13.8 to 99999)
    6.3 (4.9 to 12.2)
    Statistical analysis title
    Talazoparib versus Physician's Choice Treatment
    Statistical analysis description
    Hazard ratio is based on stratified Cox regression model with treatment as the only covariate (stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system).
    Comparison groups
    Talazoparib v Physician's Choice Treatment
    Number of subjects included in analysis
    376
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.376
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.257
         upper limit
    0.549

    Other pre-specified: Time to Deterioration (TTD) in Breast Symptoms Scale as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23)

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    End point title
    Time to Deterioration (TTD) in Breast Symptoms Scale as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23)
    End point description
    TTD was defined as the time from randomization to the first observation with a>=10 point increase and no subsequent observations with a <10 point increase from baseline in breast symptom score based on the EORTC-QLQ-BR23. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of subjects with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much) within each scale. PRO-evaluable population included all subjects who completed the PRO questionnaire at baseline and at least 1 visit postbaseline. Here, 99999 = median and 95% CI was not estimable due to the low number of subjects with event.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to a maximum duration of 36.9 months
    End point values
    Talazoparib Physician's Choice Treatment
    Number of subjects analysed
    262
    114
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (10.3 to 99999)
    Statistical analysis title
    Talazoparib versus Physician's Choice Treatment
    Comparison groups
    Talazoparib v Physician's Choice Treatment
    Number of subjects included in analysis
    376
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0053
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.392
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.198
         upper limit
    0.775

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Talazoparib: Baseline up to a maximum duration of 71.3 months; Physician’s Choice Treatment: Baseline up to maximum duration of 46.1 months
    Adverse event reporting additional description
    Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    v20.0
    Reporting groups
    Reporting group title
    Physician's Choice Treatment
    Reporting group description
    Subjects received 1 of the following drugs in specified regimens, as per the physician’s choice: 1) capecitabine 1250 mg/m^2 orally twice daily on Day 1 to 14 in each cycle; 2) eribulin mesylate 1.4 mg/m^2 (equivalent to eribulin 1.23 mg/ m^2), as 2 to 5 minute IV infusion on Day 1 and 8 in each cycle; 3) gemcitabine 1250 mg/m^2 as 30-minute IV infusion on Day 1 and 8 in each cycle; 4) vinorelbine 30 mg/m^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 in each cycle; until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 45.3 months). One cycle was of 21 days.

    Reporting group title
    Talazoparib
    Reporting group description
    Subjects received talazoparib 1 mg, orally, once daily, until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician’s decision to terminate treatment, or Sponsor’s decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.

    Serious adverse events
    Physician's Choice Treatment Talazoparib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    39 / 126 (30.95%)
    103 / 286 (36.01%)
         number of deaths (all causes)
    100
    220
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system
         subjects affected / exposed
    0 / 126 (0.00%)
    4 / 286 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to pancreas
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute promyelocytic leukaemia
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Second primary malignancy
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis malignant
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 126 (1.59%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Breast reconstruction
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salpingo-oophorectomy
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenectomy
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 126 (1.59%)
    8 / 286 (2.80%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 126 (1.59%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Discomfort
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised oedema
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Bartholin's cyst
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    7 / 126 (5.56%)
    4 / 286 (1.40%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 126 (0.00%)
    4 / 286 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 126 (0.00%)
    6 / 286 (2.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumopathy
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed mood
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 126 (0.00%)
    4 / 286 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 126 (1.59%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    6 / 6
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scar
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 126 (0.00%)
    3 / 286 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 126 (0.00%)
    5 / 286 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 126 (0.79%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neurological symptom
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Syncope
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    2 / 126 (1.59%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 126 (0.00%)
    18 / 286 (6.29%)
         occurrences causally related to treatment / all
    0 / 0
    20 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 126 (3.17%)
    3 / 286 (1.05%)
         occurrences causally related to treatment / all
    4 / 4
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    2 / 126 (1.59%)
    5 / 286 (1.75%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 126 (1.59%)
    3 / 286 (1.05%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 126 (0.79%)
    3 / 286 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 126 (2.38%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 126 (1.59%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Liver disorder
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Venoocclusive liver disease
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cholecystitis
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Scar pain
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 126 (0.79%)
    5 / 286 (1.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 126 (1.59%)
    3 / 286 (1.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cellulitis
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mycobacterium avium complex infection
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 286 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 126 (0.00%)
    2 / 286 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 126 (1.59%)
    0 / 286 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Physician's Choice Treatment Talazoparib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    123 / 126 (97.62%)
    282 / 286 (98.60%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    9 / 126 (7.14%)
    23 / 286 (8.04%)
         occurrences all number
    9
    30
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    12 / 126 (9.52%)
    45 / 286 (15.73%)
         occurrences all number
    17
    103
    Fatigue
         subjects affected / exposed
    54 / 126 (42.86%)
    147 / 286 (51.40%)
         occurrences all number
    97
    260
    Pyrexia
         subjects affected / exposed
    21 / 126 (16.67%)
    31 / 286 (10.84%)
         occurrences all number
    34
    45
    Oedema peripheral
         subjects affected / exposed
    8 / 126 (6.35%)
    23 / 286 (8.04%)
         occurrences all number
    14
    28
    Mucosal inflammation
         subjects affected / exposed
    9 / 126 (7.14%)
    16 / 286 (5.59%)
         occurrences all number
    11
    19
    Influenza like illness
         subjects affected / exposed
    2 / 126 (1.59%)
    20 / 286 (6.99%)
         occurrences all number
    2
    33
    Non-cardiac chest pain
         subjects affected / exposed
    5 / 126 (3.97%)
    17 / 286 (5.94%)
         occurrences all number
    6
    18
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    19 / 126 (15.08%)
    54 / 286 (18.88%)
         occurrences all number
    25
    88
    Cough
         subjects affected / exposed
    20 / 126 (15.87%)
    65 / 286 (22.73%)
         occurrences all number
    24
    102
    Oropharyngeal pain
         subjects affected / exposed
    10 / 126 (7.94%)
    28 / 286 (9.79%)
         occurrences all number
    16
    34
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    10 / 126 (7.94%)
    38 / 286 (13.29%)
         occurrences all number
    10
    47
    Depression
         subjects affected / exposed
    4 / 126 (3.17%)
    24 / 286 (8.39%)
         occurrences all number
    4
    28
    Anxiety
         subjects affected / exposed
    9 / 126 (7.14%)
    24 / 286 (8.39%)
         occurrences all number
    10
    29
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    18 / 126 (14.29%)
    30 / 286 (10.49%)
         occurrences all number
    42
    98
    Weight decreased
         subjects affected / exposed
    15 / 126 (11.90%)
    23 / 286 (8.04%)
         occurrences all number
    19
    33
    Aspartate aminotransferase increased
         subjects affected / exposed
    15 / 126 (11.90%)
    15 / 286 (5.24%)
         occurrences all number
    29
    21
    White blood cell count decreased
         subjects affected / exposed
    5 / 126 (3.97%)
    32 / 286 (11.19%)
         occurrences all number
    7
    86
    Platelet count decreased
         subjects affected / exposed
    4 / 126 (3.17%)
    36 / 286 (12.59%)
         occurrences all number
    7
    128
    Alanine aminotransferase increased
         subjects affected / exposed
    15 / 126 (11.90%)
    11 / 286 (3.85%)
         occurrences all number
    26
    14
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    13 / 126 (10.32%)
    51 / 286 (17.83%)
         occurrences all number
    17
    69
    Headache
         subjects affected / exposed
    29 / 126 (23.02%)
    96 / 286 (33.57%)
         occurrences all number
    39
    146
    Dysgeusia
         subjects affected / exposed
    11 / 126 (8.73%)
    30 / 286 (10.49%)
         occurrences all number
    12
    39
    Paraesthesia
         subjects affected / exposed
    15 / 126 (11.90%)
    13 / 286 (4.55%)
         occurrences all number
    20
    16
    Peripheral sensory neuropathy
         subjects affected / exposed
    7 / 126 (5.56%)
    2 / 286 (0.70%)
         occurrences all number
    8
    3
    Neuropathy peripheral
         subjects affected / exposed
    9 / 126 (7.14%)
    19 / 286 (6.64%)
         occurrences all number
    10
    23
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    24 / 126 (19.05%)
    153 / 286 (53.50%)
         occurrences all number
    57
    746
    Thrombocytopenia
         subjects affected / exposed
    7 / 126 (5.56%)
    50 / 286 (17.48%)
         occurrences all number
    10
    140
    Neutropenia
         subjects affected / exposed
    36 / 126 (28.57%)
    77 / 286 (26.92%)
         occurrences all number
    113
    279
    Leukopenia
         subjects affected / exposed
    12 / 126 (9.52%)
    24 / 286 (8.39%)
         occurrences all number
    43
    70
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    9 / 126 (7.14%)
    10 / 286 (3.50%)
         occurrences all number
    10
    11
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    60 / 126 (47.62%)
    142 / 286 (49.65%)
         occurrences all number
    100
    228
    Diarrhoea
         subjects affected / exposed
    32 / 126 (25.40%)
    68 / 286 (23.78%)
         occurrences all number
    77
    139
    Vomiting
         subjects affected / exposed
    28 / 126 (22.22%)
    74 / 286 (25.87%)
         occurrences all number
    47
    126
    Abdominal pain
         subjects affected / exposed
    18 / 126 (14.29%)
    36 / 286 (12.59%)
         occurrences all number
    24
    50
    Constipation
         subjects affected / exposed
    28 / 126 (22.22%)
    66 / 286 (23.08%)
         occurrences all number
    47
    89
    Dyspepsia
         subjects affected / exposed
    10 / 126 (7.94%)
    33 / 286 (11.54%)
         occurrences all number
    14
    41
    Stomatitis
         subjects affected / exposed
    7 / 126 (5.56%)
    24 / 286 (8.39%)
         occurrences all number
    11
    36
    Dry mouth
         subjects affected / exposed
    8 / 126 (6.35%)
    19 / 286 (6.64%)
         occurrences all number
    9
    25
    Abdominal pain upper
         subjects affected / exposed
    5 / 126 (3.97%)
    28 / 286 (9.79%)
         occurrences all number
    6
    33
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    35 / 126 (27.78%)
    78 / 286 (27.27%)
         occurrences all number
    37
    87
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    28 / 126 (22.22%)
    4 / 286 (1.40%)
         occurrences all number
    71
    5
    Dry skin
         subjects affected / exposed
    9 / 126 (7.14%)
    14 / 286 (4.90%)
         occurrences all number
    10
    20
    Rash
         subjects affected / exposed
    12 / 126 (9.52%)
    29 / 286 (10.14%)
         occurrences all number
    18
    37
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    14 / 126 (11.11%)
    45 / 286 (15.73%)
         occurrences all number
    20
    62
    Back pain
         subjects affected / exposed
    19 / 126 (15.08%)
    67 / 286 (23.43%)
         occurrences all number
    28
    104
    Arthralgia
         subjects affected / exposed
    15 / 126 (11.90%)
    55 / 286 (19.23%)
         occurrences all number
    18
    95
    Musculoskeletal chest pain
         subjects affected / exposed
    9 / 126 (7.14%)
    28 / 286 (9.79%)
         occurrences all number
    9
    33
    Musculoskeletal pain
         subjects affected / exposed
    9 / 126 (7.14%)
    29 / 286 (10.14%)
         occurrences all number
    9
    36
    Myalgia
         subjects affected / exposed
    14 / 126 (11.11%)
    25 / 286 (8.74%)
         occurrences all number
    22
    33
    Bone pain
         subjects affected / exposed
    7 / 126 (5.56%)
    15 / 286 (5.24%)
         occurrences all number
    11
    18
    Neck pain
         subjects affected / exposed
    6 / 126 (4.76%)
    17 / 286 (5.94%)
         occurrences all number
    6
    24
    Muscle spasms
         subjects affected / exposed
    3 / 126 (2.38%)
    18 / 286 (6.29%)
         occurrences all number
    5
    25
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 126 (10.32%)
    41 / 286 (14.34%)
         occurrences all number
    14
    61
    Viral upper respiratory tract infection
         subjects affected / exposed
    8 / 126 (6.35%)
    35 / 286 (12.24%)
         occurrences all number
    8
    56
    Urinary tract infection
         subjects affected / exposed
    3 / 126 (2.38%)
    30 / 286 (10.49%)
         occurrences all number
    5
    42
    Sinusitis
         subjects affected / exposed
    4 / 126 (3.17%)
    21 / 286 (7.34%)
         occurrences all number
    6
    25
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    28 / 126 (22.22%)
    62 / 286 (21.68%)
         occurrences all number
    32
    93

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Jun 2019
    1. Change in study visit frequency and study procedures as final OS analysis was achieved.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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