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    Clinical Trial Results:
    A RANDOMIZED, OPEN-LABEL, MULTI-CENTER PHASE IV STUDY EVALUATING PALBOCICLIB PLUS ENDOCRINE TREATMENT VERSUS A CHEMOTHERAPY-BASED TREATMENT STRATEGY IN PATIENTS WITH HORMONE RECEPTOR POSITIVE / HER2 NEGATIVE METASTATIC BREAST CANCER IN A REAL WORLD SETTING.

    Summary
    EudraCT number
    		 2016-004482-89
    Trial protocol
    		 DE  
    Global end of trial date
    30 Aug 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Aug 2025
    First version publication date
    15 Aug 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GBG93
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 BfArM number: 4042230, ClinicalTrials.gov: NCT03355157
    Sponsors
    Sponsor organisation name
    GBG Forschungs GmbH
    Sponsor organisation address
    Dornhofstr. 10, Neu-Isenburg, Germany, 63263
    Public contact
    Medicine and Research, GBG Forschungs GmbH, +49 610274800, publications@gbg.de
    Scientific contact
    Medicine and Research, GBG Forschungs GmbH, +49 610274800, publications@gbg.de
    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
    06 Jun 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Jul 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Aug 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the time-to-treatment failure (TTF) for patients randomized to receive pre-defined chemotherapy treatment strategy versus those randomized to receive palbociclib and endocrine therapy.
    Protection of trial subjects
    The trial protocol including amendments, the patient information and the informed consent were reviewed and approved from a properly constituted IRB/IEC for each site prior to the study start. The trial was in compliance with the International Conference on Harmonization (ICH) - Harmonized Tripartite Guideline for Good Clinical Practice (GCP) (E6), and the Commission Directives in the European Community as well as with the applicable German national laws and regulations, and with Declaration of Helsinki and its revisions in all aspects of preparation, monitoring, reporting, auditing, and archiving.
    Background therapy
    		 in palbociclib arm: endocrine treatment by Aromatase inhibitors (exemestane or letrozole) or fulvestrant as per label in the respective country in comparator arm: physicians choice mono-chemotherapy (capecitabine, epirubicin, paclitaxel or vinorelbine i.v.; having either an approved label in the respective countries and/or is supported by guidelines for the treatment of first-line MBC) with or without an endocrine maintenance therapy after chemotherapy with Tamoxifen, aromatase inhibitors (exemestane or letrozole) or fulvestrant as per label in the respective country.
    Evidence for comparator
    		 no comparator drug
    Actual start date of recruitment
    30 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 130
    Worldwide total number of subjects
    130
    EEA total number of subjects
    130
    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)
    75
    From 65 to 84 years
    53
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 Study run only in Germany, 28 sites recruited 130 patients. Start of recruitment = April 2018 First Pat in = 17-Apr-2018 Last Pat in = 15-Dec-2023 Last Pat completed = 1-Aug-2024 65 Pat randomized to each study arm 10 Pat revoke consent prior to treatment 61 Pat in arm: palbociclib + estrogen therapy 59 Pat in arm: chemotherapy

    Pre-assignment
    Screening details
    		 Fe/male pat’s with histol. confirmed symptomatic/asymptomatic metastatic invasive HR+ and HER2 neg breast cancer, excluding asymptom. oligometastases of bone as the only site of metastatic disease; pat’s have a life-expectancy >6 months and in opinion of treating physician are candidates suitable for randomization for mono-chem. therapy treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Palbociclib + endocrine therapy
    Arm description
    		 Palbociclib 125mg, hard capsules + Endocrine Therapy (ET) ET: aromatase inhibitors exemestane or letrozole or fulvestrant as per label in the respective countries. Letrozole 2.5 mg orally once a day Exemestane 25 mg orally once a day Fulvestrant 2x 250 mg injections i.m. on Day 1 and Day 15 in the first month followed by 2x 250 mg on Day 1 every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Palbociclib 125mg, hard capsules
    Investigational medicinal product code
    100000163078
    Other name
    Ibrance
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Palbociclib hard capsules, at a dose of 125 mg, orally, once a day, at the same day time, with food for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days.

    Arm title
    		 Chemotherapy +/- endocrine maintenance therapy
    Arm description
    		 Physician´s choice mono-chemotherapy (capecitabine, epirubicin, paclitaxel or vinorelbine i.v.) having either an approved label in the respective countries and/or is supported by guidelines for the treatment of first-line metastatic breast cancer. Endocrine therapy as maintenance therapy after chemotherapy: Tamoxifen, aromatase inhibitors (exemestane or letrozole) or fulvestrant as per label in the respective countries.
    Arm type
    		 Physician´s choice mono-chemotherap

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Started
    65
    65
    Completed
    15
    4
    Not completed
    50
    61
         Initiation of altern/prohibited anti-cancer therap
    -
    2
         Death
    5
    2
         never started treatment
    4
    6
         Second primary of non-breast cancers
    1
    -
         Adverse event
    3
    2
         Patient's decision
    5
    5
         patient got lost
    -
    1
         Progressive disease
    32
    42
         Use of radiotherapy not indicated at baseline
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Palbociclib + endocrine therapy
    Reporting group description
    		 Palbociclib 125mg, hard capsules + Endocrine Therapy (ET) ET: aromatase inhibitors exemestane or letrozole or fulvestrant as per label in the respective countries. Letrozole 2.5 mg orally once a day Exemestane 25 mg orally once a day Fulvestrant 2x 250 mg injections i.m. on Day 1 and Day 15 in the first month followed by 2x 250 mg on Day 1 every 4 weeks

    Reporting group title
    Chemotherapy +/- endocrine maintenance therapy
    Reporting group description
    		 Physician´s choice mono-chemotherapy (capecitabine, epirubicin, paclitaxel or vinorelbine i.v.) having either an approved label in the respective countries and/or is supported by guidelines for the treatment of first-line metastatic breast cancer. Endocrine therapy as maintenance therapy after chemotherapy: Tamoxifen, aromatase inhibitors (exemestane or letrozole) or fulvestrant as per label in the respective countries.

    Reporting group values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy Total
    Number of subjects
    		 65 65 130
    Age categorical
    Units: Subjects
    Age continuous
    age at randomization
    Units: years
        median (full range (min-max))
    		 63 (42 to 85) 62 (31 to 80) -
    Gender categorical
    gender at randomization
    Units: Subjects
        Female
    		 64 63 127
        Male
    		 1 2 3

    End points

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    End points reporting groups
    Reporting group title
    Palbociclib + endocrine therapy
    Reporting group description
    		 Palbociclib 125mg, hard capsules + Endocrine Therapy (ET) ET: aromatase inhibitors exemestane or letrozole or fulvestrant as per label in the respective countries. Letrozole 2.5 mg orally once a day Exemestane 25 mg orally once a day Fulvestrant 2x 250 mg injections i.m. on Day 1 and Day 15 in the first month followed by 2x 250 mg on Day 1 every 4 weeks

    Reporting group title
    Chemotherapy +/- endocrine maintenance therapy
    Reporting group description
    		 Physician´s choice mono-chemotherapy (capecitabine, epirubicin, paclitaxel or vinorelbine i.v.) having either an approved label in the respective countries and/or is supported by guidelines for the treatment of first-line metastatic breast cancer. Endocrine therapy as maintenance therapy after chemotherapy: Tamoxifen, aromatase inhibitors (exemestane or letrozole) or fulvestrant as per label in the respective countries.

    Primary: Time to treatment failure (TTF), mITT analysis set

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    End point title
    		 Time to treatment failure (TTF), mITT analysis set
    End point description
    Treatment failure rate (TF) at 6 months. Intercurrent events: - change of endocrine maintenance therapy (change within the class of aromatase inhibitors was not considered as a TF) - prohibited anticancer medication was used - use of radiotherapy - pat switched from palbo+ET to CT arm or vice versa - pat was lost during study treatment - change from one mono-CT agent to another or the use of poly-chemotherapy (change of CT before start of treatment, or extension of CT treatment compared to the initial treatment plan was not considered as TF) Also, the discontinuation due to investigator’s decision was not considered as TF.
    End point type
    Primary
    End point timeframe
    TTF was defined as time from randomization to treatment failure due to disease progression, treatment toxicity, patient’s preference, or death or intercurrent event (refer to description).
    End point values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Number of subjects analysed
    61
    59
    Units: percent
        number (confidence interval 80%)
    66.7 (58.2 to 73.8)
    50.8 (42.2 to 58.8)
    Statistical analysis title
    		 Hazard ratio
    Statistical analysis description
    Additionally, the 95% CI for the hazard ratio was provided: hazard ratio = 0.46 (95% CI, 0.31, 0.69).
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.46
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.6
    Statistical analysis title
    		 Two-sided log-rank test
    Statistical analysis description
    The difference in TTF was tested using a two-sided log-rank test with significance level of alpha = 0.2 .
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002
    Method
    		 Logrank
    Confidence interval

    Secondary: Time to first subsequent treatment (TFST), mITT analysis set

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    End point title
    		 Time to first subsequent treatment (TFST), mITT analysis set
    End point description
    Time to first subsequent treatment (TFST) was defined as the time from randomization to start of first subsequent anticancer treatment or death. Note: anticancer treatment actually comprised all sorts of treatment such as ET, chemotherapy, targeted therapy etc.
    End point type
    Secondary
    End point timeframe
    Time from randomization to first subsequent anticancer treatment (including chemotherapy, endocrine or targeted therapy) after EOT, or death.
    End point values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Number of subjects analysed
    61
    59
    Units: percent
        number (confidence interval 80%)
    78.2 (70.3 to 84.2)
    68.4 (59.8 to 75.6)
    Statistical analysis title
    		 Hazard ratio
    Statistical analysis description
    Additionally, the 95% CI for the hazard ratio was provided: hazard ratio = 0.50 (95% CI, 0.32, 0.77).
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 0.66
    Statistical analysis title
    		 Two-sided log-rank test
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0015
    Method
    		 Logrank
    Confidence interval

    Secondary: Time to first subsequent chemotherapy (TFSCT), mITT analysis set

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    End point title
    		 Time to first subsequent chemotherapy (TFSCT), mITT analysis set
    End point description
    Restricted mean survival time (RMST) for TFSCT in months. The proportional hazard assumption is violated for TFSCT; therefore, the hazard ratio may not be an adequate measure of effect, and the log-rank test was not an appropriate test here. Instead, the restricted mean survival time (RMST) until tau=38 months with the corresponding adequate test (Wald-type test using an approximate Chi-square statistic) for comparison of the RMST between treatment arms was performed. Tau was chosen according to the smaller maximum observation time of an event in both arms. The RMST, the area under the survival curve between 0 and tau=38 months, is the estimate of the mean survival time in this time interval.
    End point type
    Secondary
    End point timeframe
    Time from randomization to start of first subsequent anticancer chemotherapy or death (TFSCT).
    End point values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Number of subjects analysed
    61
    59
    Units: percent
        number (confidence interval 95%)
    23.9 (20.1 to 27.6)
    25.0 (21.3 to 28.6)
    Statistical analysis title
    		 Test for comparison of RMST
    Statistical analysis description
    The restricted mean survival time (RMST) until tau=38 months with the corresponding adequate test (Wald-type test using an approximate Chi-square statistic) for comparison of the RMST between treatment arms was performed. Tau was chosen according to the smaller maximum observation time of an event in both arms. The RMST, the area under the survival curve between 0 and tau=38 months, is the estimate of the mean survival time in this time interval.
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6744
    Method
    		 Wald-type test
    Confidence interval

    Secondary: Time to second subsequent treatment regimen (TSST), mITT analysis set

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    End point title
    		 Time to second subsequent treatment regimen (TSST), mITT analysis set
    End point description
    Restricted mean survival time (RMST) for TSST in months. The proportional hazard assumption is violated for TSST; therefore, the hazard ratio may not be an adequate measure of effect and the log-rank test not an appropriate test here. Instead, the restricted mean survival time (RMST) until tau=35 months with the corresponding adequate test (Wald-type test using an approximate Chi-square statistic) for comparison of the RMST between treatment arms was performed. Tau was chosen according to the smaller maximum observation time of an event in both arms. The RMST, the area under the survival curve between 0 and tau=35 months, is the estimate of the mean survival time in this time interval.
    End point type
    Secondary
    End point timeframe
    Time from randomization to start of second subsequent treatment regimen (TSST) or death.
    End point values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Number of subjects analysed
    61
    59
    Units: percent
        number (confidence interval 95%)
    24.9 (21.7 to 28.1)
    21.5 (18.3 to 24.6)
    Statistical analysis title
    		 Test for comparison of RMST
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1332
    Method
    		 Wald-type test
    Confidence interval

    Secondary: Overall Survival (OS), mITT analysis set

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    End point title
    		 Overall Survival (OS), mITT analysis set
    End point description
    Restricted mean survival time (RMST) for OS in months. The proportional hazard assumption is violated for OS; therefore, the hazard ratio may not be an adequate measure of effect and the log-rank test not an appropriate test here. Instead, the RMST until tau=46 months with the corresponding adequate test (Wald-type test using an approximate Chi-square statistic) for comparison of the RMST between treatment arms was performed. Tau was chosen according to the smaller maximum observation time of an event in both arms. The RMST, the area under the survival curve between 0 and tau=46 months, is the estimate of the mean survival time in this time interval.
    End point type
    Secondary
    End point timeframe
    OS is defined as the time from randomization to death due to any reason.
    End point values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Number of subjects analysed
    61
    59
    Units: percent
        number (confidence interval 95%)
    33.6 (29.3 to 37.9)
    31.5 (27.1 to 35.9)
    Statistical analysis title
    		 Test for comparison of RMST
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4939
    Method
    		 Wald-type test
    Confidence interval

    Secondary: Progression free survival (PFS), mITT analysis set

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    End point title
    		 Progression free survival (PFS), mITT analysis set
    End point description
    End point type
    Secondary
    End point timeframe
    Progression free survival (PFS) is the time from randomization to first progression as assessed by the investigator or death, whichever occurs first.
    End point values
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Number of subjects analysed
    61
    59
    Units: percent
        number (confidence interval 80%)
    71.5 (63.2 to 78.2)
    63.0 (54.2 to 70.6)
    Statistical analysis title
    		 Hazard ratio
    Statistical analysis description
    Additionally, the 95% CI for the hazard ratio was provided: hazard ratio = 0.45 (95% CI, 0.29, 0.70).
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.45
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 0.6
    Statistical analysis title
    		 Two-sided log-rank test
    Comparison groups
    Palbociclib + endocrine therapy v Chemotherapy +/- endocrine maintenance therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002
    Method
    		 Logrank
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events occurring during the study treatment until 30 days after the last study treatment were reported. AEs were analyzed according to MedDRA V24 as any grade (1-4) and high-grade (3-4).
    Adverse event reporting additional description
    Safety analysis was performed based on the safety analysis set, which consists of 62 patients who were treated with Palbociclib and 58 patients who were treated with chemotherapy. One patient was randomized in CT arm but was treated with palbociclib from the beginning.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24
    Reporting groups
    Reporting group title
    Palbociclib + endocrine therapy
    Reporting group description
    		 The occurrence of AE categories was displayed as • number and percentage of grades 1-4 (any grade) per treatment group and overall, • number and percentage of grades 3-4 (high grade) per treatment group and overall, • number and percentage of patients per grade (none, grade 1, grade 2, grade 3, grade 4) per treatment group and overall.

    Reporting group title
    Chemotherapy +/- endocrine maintenance therapy
    Reporting group description
    		 The occurrence of AE categories was displayed as • number and percentage of grades 1-4 (any grade) per treatment group and overall, • number and percentage of grades 3-4 (high grade) per treatment group and overall, • number and percentage of patients per grade (none, grade 1, grade 2, grade 3, grade 4) per treatment group and overall.

    Serious adverse events
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 62 (29.03%)
    16 / 58 (27.59%)
         number of deaths (all causes)
    25
    24
         number of deaths resulting from adverse events
    6
    0
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 62 (4.84%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Lymphadenectomy
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (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
    Chest pain
         subjects affected / exposed
    1 / 62 (1.61%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fibula fracture
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    3 / 62 (4.84%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 62 (3.23%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 62 (3.23%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 62 (1.61%)
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 62 (1.61%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 62 (3.23%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis intestinalis
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 62 (4.84%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         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
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected seroma
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 58 (1.72%)
         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 / 62 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 62 (3.23%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    		 Palbociclib + endocrine therapy Chemotherapy +/- endocrine maintenance therapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    61 / 62 (98.39%)
    58 / 58 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Other SOC 02
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Embolism
         subjects affected / exposed
    4 / 62 (6.45%)
    4 / 58 (6.90%)
         occurrences all number
    4
    4
    Hot flush
         subjects affected / exposed
    18 / 62 (29.03%)
    6 / 58 (10.34%)
         occurrences all number
    18
    6
    Hypertension
         subjects affected / exposed
    3 / 62 (4.84%)
    3 / 58 (5.17%)
         occurrences all number
    3
    3
    Other SOC 12
         subjects affected / exposed
    2 / 62 (3.23%)
    2 / 58 (3.45%)
         occurrences all number
    2
    2
    Surgical and medical procedures
    Other SOC 25
         subjects affected / exposed
    5 / 62 (8.06%)
    1 / 58 (1.72%)
         occurrences all number
    5
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    41 / 62 (66.13%)
    42 / 58 (72.41%)
         occurrences all number
    41
    42
    Oedema peripheral
         subjects affected / exposed
    9 / 62 (14.52%)
    12 / 58 (20.69%)
         occurrences all number
    9
    12
    Pyrexia
         subjects affected / exposed
    4 / 62 (6.45%)
    2 / 58 (3.45%)
         occurrences all number
    4
    2
    Pain
         subjects affected / exposed
    4 / 62 (6.45%)
    5 / 58 (8.62%)
         occurrences all number
    4
    5
    Other SOC 22
         subjects affected / exposed
    11 / 62 (17.74%)
    6 / 58 (10.34%)
         occurrences all number
    11
    6
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 62 (0.00%)
    4 / 58 (6.90%)
         occurrences all number
    0
    4
    Reproductive system and breast disorders
    Vulvovaginal dryness
         subjects affected / exposed
    2 / 62 (3.23%)
    2 / 58 (3.45%)
         occurrences all number
    2
    2
    Other SOC 20
         subjects affected / exposed
    3 / 62 (4.84%)
    2 / 58 (3.45%)
         occurrences all number
    3
    2
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    7 / 62 (11.29%)
    7 / 58 (12.07%)
         occurrences all number
    7
    7
    Dyspnoea
         subjects affected / exposed
    19 / 62 (30.65%)
    21 / 58 (36.21%)
         occurrences all number
    19
    21
    Cough
         subjects affected / exposed
    13 / 62 (20.97%)
    11 / 58 (18.97%)
         occurrences all number
    13
    11
    Pneumonitis
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences all number
    1
    0
    Pleural effusion
         subjects affected / exposed
    4 / 62 (6.45%)
    6 / 58 (10.34%)
         occurrences all number
    4
    6
    Pleuritic pain
         subjects affected / exposed
    1 / 62 (1.61%)
    1 / 58 (1.72%)
         occurrences all number
    1
    1
    Nasal dryness
         subjects affected / exposed
    4 / 62 (6.45%)
    2 / 58 (3.45%)
         occurrences all number
    4
    2
    Other SOC 13
         subjects affected / exposed
    1 / 62 (1.61%)
    5 / 58 (8.62%)
         occurrences all number
    1
    5
    Psychiatric disorders
    Depression
         subjects affected / exposed
    3 / 62 (4.84%)
    5 / 58 (8.62%)
         occurrences all number
    3
    5
    Insomnia
         subjects affected / exposed
    6 / 62 (9.68%)
    2 / 58 (3.45%)
         occurrences all number
    6
    2
    Sleep disorder
         subjects affected / exposed
    6 / 62 (9.68%)
    6 / 58 (10.34%)
         occurrences all number
    6
    6
    Other SOC 07
         subjects affected / exposed
    5 / 62 (8.06%)
    5 / 58 (8.62%)
         occurrences all number
    5
    5
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    27 / 62 (43.55%)
    35 / 58 (60.34%)
         occurrences all number
    27
    35
    Alanine aminotransferase increased
         subjects affected / exposed
    26 / 62 (41.94%)
    27 / 58 (46.55%)
         occurrences all number
    26
    27
    Aspartate aminotransferase increased
         subjects affected / exposed
    34 / 62 (54.84%)
    35 / 58 (60.34%)
         occurrences all number
    34
    35
    Blood bilirubin increased
         subjects affected / exposed
    7 / 62 (11.29%)
    11 / 58 (18.97%)
         occurrences all number
    7
    11
    Blood creatinine increased
         subjects affected / exposed
    20 / 62 (32.26%)
    19 / 58 (32.76%)
         occurrences all number
    20
    19
    Blood albumin decreased
         subjects affected / exposed
    10 / 62 (16.13%)
    9 / 58 (15.52%)
         occurrences all number
    10
    9
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    5 / 62 (8.06%)
    2 / 58 (3.45%)
         occurrences all number
    5
    2
    Other SOC 23
         subjects affected / exposed
    8 / 62 (12.90%)
    2 / 58 (3.45%)
         occurrences all number
    8
    2
    Injury, poisoning and procedural complications
    Other SOC 24
         subjects affected / exposed
    10 / 62 (16.13%)
    1 / 58 (1.72%)
         occurrences all number
    10
    1
    Cardiac disorders
    Other SOC 11
         subjects affected / exposed
    2 / 62 (3.23%)
    2 / 58 (3.45%)
         occurrences all number
    2
    2
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    4 / 62 (6.45%)
    10 / 58 (17.24%)
         occurrences all number
    4
    10
    Headache
         subjects affected / exposed
    10 / 62 (16.13%)
    8 / 58 (13.79%)
         occurrences all number
    10
    8
    Cognitive disorder
         subjects affected / exposed
    6 / 62 (9.68%)
    2 / 58 (3.45%)
         occurrences all number
    6
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    14 / 62 (22.58%)
    21 / 58 (36.21%)
         occurrences all number
    14
    21
    Nervous system disorder
         subjects affected / exposed
    7 / 62 (11.29%)
    9 / 58 (15.52%)
         occurrences all number
    7
    9
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    49 / 62 (79.03%)
    35 / 58 (60.34%)
         occurrences all number
    49
    35
    Leukopenia
         subjects affected / exposed
    59 / 62 (95.16%)
    31 / 58 (53.45%)
         occurrences all number
    59
    31
    Thrombocytopenia
         subjects affected / exposed
    29 / 62 (46.77%)
    14 / 58 (24.14%)
         occurrences all number
    29
    14
    Neutropenia
         subjects affected / exposed
    56 / 62 (90.32%)
    14 / 58 (24.14%)
         occurrences all number
    56
    14
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    6 / 62 (9.68%)
    9 / 58 (15.52%)
         occurrences all number
    6
    9
    Other SOC 10
         subjects affected / exposed
    1 / 62 (1.61%)
    0 / 58 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 62 (1.61%)
    1 / 58 (1.72%)
         occurrences all number
    1
    1
    Dry eye
         subjects affected / exposed
    4 / 62 (6.45%)
    6 / 58 (10.34%)
         occurrences all number
    4
    6
    Other SOC 09
         subjects affected / exposed
    4 / 62 (6.45%)
    3 / 58 (5.17%)
         occurrences all number
    4
    3
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    22 / 62 (35.48%)
    32 / 58 (55.17%)
         occurrences all number
    22
    32
    Vomiting
         subjects affected / exposed
    9 / 62 (14.52%)
    18 / 58 (31.03%)
         occurrences all number
    9
    18
    Stomatitis
         subjects affected / exposed
    11 / 62 (17.74%)
    11 / 58 (18.97%)
         occurrences all number
    11
    11
    Dyspepsia
         subjects affected / exposed
    6 / 62 (9.68%)
    10 / 58 (17.24%)
         occurrences all number
    6
    10
    Constipation
         subjects affected / exposed
    9 / 62 (14.52%)
    10 / 58 (17.24%)
         occurrences all number
    9
    10
    Diarrhoea
         subjects affected / exposed
    10 / 62 (16.13%)
    21 / 58 (36.21%)
         occurrences all number
    10
    21
    Gastrointestinal pain
         subjects affected / exposed
    4 / 62 (6.45%)
    10 / 58 (17.24%)
         occurrences all number
    4
    10
    Flatulence
         subjects affected / exposed
    2 / 62 (3.23%)
    4 / 58 (6.90%)
         occurrences all number
    2
    4
    Ascites
         subjects affected / exposed
    2 / 62 (3.23%)
    0 / 58 (0.00%)
         occurrences all number
    2
    0
    Other SOC 14
         subjects affected / exposed
    13 / 62 (20.97%)
    11 / 58 (18.97%)
         occurrences all number
    13
    11
    Hepatobiliary disorders
    Other SOC 15
         subjects affected / exposed
    1 / 62 (1.61%)
    3 / 58 (5.17%)
         occurrences all number
    1
    3
    Skin and subcutaneous tissue disorders
    Skin reaction
         subjects affected / exposed
    16 / 62 (25.81%)
    17 / 58 (29.31%)
         occurrences all number
    16
    17
    Alopecia
         subjects affected / exposed
    16 / 62 (25.81%)
    16 / 58 (27.59%)
         occurrences all number
    16
    16
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    3 / 62 (4.84%)
    17 / 58 (29.31%)
         occurrences all number
    3
    17
    Dry skin
         subjects affected / exposed
    3 / 62 (4.84%)
    3 / 58 (5.17%)
         occurrences all number
    3
    3
    Nail disorder
         subjects affected / exposed
    2 / 62 (3.23%)
    7 / 58 (12.07%)
         occurrences all number
    2
    7
    Other SOC 16
         subjects affected / exposed
    10 / 62 (16.13%)
    5 / 58 (8.62%)
         occurrences all number
    10
    5
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    4 / 62 (6.45%)
    2 / 58 (3.45%)
         occurrences all number
    4
    2
    Other SOC 18
         subjects affected / exposed
    4 / 62 (6.45%)
    3 / 58 (5.17%)
         occurrences all number
    4
    3
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    21 / 62 (33.87%)
    22 / 58 (37.93%)
         occurrences all number
    21
    22
    Arthralgia
         subjects affected / exposed
    22 / 62 (35.48%)
    19 / 58 (32.76%)
         occurrences all number
    22
    19
    Myalgia
         subjects affected / exposed
    11 / 62 (17.74%)
    13 / 58 (22.41%)
         occurrences all number
    11
    13
    Back pain
         subjects affected / exposed
    5 / 62 (8.06%)
    9 / 58 (15.52%)
         occurrences all number
    5
    9
    Pain in extremity
         subjects affected / exposed
    7 / 62 (11.29%)
    6 / 58 (10.34%)
         occurrences all number
    7
    6
    Other SOC 17
         subjects affected / exposed
    12 / 62 (19.35%)
    11 / 58 (18.97%)
         occurrences all number
    12
    11
    Infections and infestations
    Infection
         subjects affected / exposed
    18 / 62 (29.03%)
    16 / 58 (27.59%)
         occurrences all number
    18
    16
    COVID-19
         subjects affected / exposed
    4 / 62 (6.45%)
    3 / 58 (5.17%)
         occurrences all number
    4
    3
    Influenza
         subjects affected / exposed
    3 / 62 (4.84%)
    3 / 58 (5.17%)
         occurrences all number
    3
    3
    Nasopharyngitis
         subjects affected / exposed
    5 / 62 (8.06%)
    6 / 58 (10.34%)
         occurrences all number
    5
    6
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    11 / 62 (17.74%)
    4 / 58 (6.90%)
         occurrences all number
    11
    4
    Hypocalcaemia
         subjects affected / exposed
    24 / 62 (38.71%)
    24 / 58 (41.38%)
         occurrences all number
    24
    24
    Hyperkalaemia
         subjects affected / exposed
    27 / 62 (43.55%)
    9 / 58 (15.52%)
         occurrences all number
    27
    9
    Hypokalaemia
         subjects affected / exposed
    9 / 62 (14.52%)
    8 / 58 (13.79%)
         occurrences all number
    9
    8
    Hypernatraemia
         subjects affected / exposed
    6 / 62 (9.68%)
    2 / 58 (3.45%)
         occurrences all number
    6
    2
    Hyponatraemia
         subjects affected / exposed
    18 / 62 (29.03%)
    13 / 58 (22.41%)
         occurrences all number
    18
    13
    Decreased appetite
         subjects affected / exposed
    11 / 62 (17.74%)
    11 / 58 (18.97%)
         occurrences all number
    11
    11
    Other SOC 06
         subjects affected / exposed
    2 / 62 (3.23%)
    1 / 58 (1.72%)
         occurrences all number
    2
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Jul 2018
    Amendment 1 (Version 9 - 05-JUL-2018): Reduction in the sample size from 360 to 260 patients. Change in the statistical analysis method to a modified intent-to-treat analysis, and deletion of the interim analysis without replacement. The originally planned Actiwatch as an activity tracker for day-night activity was not available to patients and was therefore excluded for operational and organizational reasons, affecting associated secondary objectives and endpoints. Additional whole blood sample (10mL) of each patient were collected before start of study treatment for NGS analysis (optional).
    08 Aug 2020
    Amendment 2 (Version 10.1 - 08-AUG-2020): The recruitment period was extended, while the sample size was further reduced from 260 to 150 patients. A report of the genetic tests on the tumor was prepared and made available to the investigator, who could then discuss the results with the patient and provide a copy of the report upon request. Patient information was adapted accordingly, as well as information regarding side effects.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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