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    Clinical Trial Results:
    A phase II, multicenter, randomized, open-label study to evaluate the safety and efficacy of 400 mg of ribociclib in combination with non-steroidal aromatase inhibitors for the treatment of pre- and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received no prior therapy for advanced disease

    Summary
    EudraCT number
    		 2018-004234-15
    Trial protocol
    		 BE   SE   CZ   FR   LT   AT   FI   DE   PT   HU   BG  
    Global end of trial date
    30 Aug 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Jul 2025
    First version publication date
    19 Jul 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CLEE011A2207
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03822468
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Lichtstrasse 35, Basel, Switzerland, 4056
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.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
    30 Aug 2024
    Is this the analysis of the primary completion data?
    No
    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
    The purpose of the study was to evaluate the safety and efficacy of a reduced ribociclib starting dose of 400 mg in combination with a non-steroidal aromatase inhibitor (NSAI) (letrozole or anastrozole) for the treatment of pre- and postmenopausal women with hormone receptor-positive (HR-positive), HER2-negative advanced breast cancer (aBC) who have received no prior therapy for advanced disease. Premenopausal women were required to receive goserelin in both treatment arms.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Jun 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 4
    Country: Number of subjects enrolled
    Austria: 14
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Brazil: 35
    Country: Number of subjects enrolled
    Bulgaria: 16
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Colombia: 22
    Country: Number of subjects enrolled
    Costa Rica: 6
    Country: Number of subjects enrolled
    Czechia: 10
    Country: Number of subjects enrolled
    Finland: 13
    Country: Number of subjects enrolled
    France: 20
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    India: 21
    Country: Number of subjects enrolled
    Jordan: 8
    Country: Number of subjects enrolled
    Lithuania: 9
    Country: Number of subjects enrolled
    Peru: 8
    Country: Number of subjects enrolled
    Portugal: 21
    Country: Number of subjects enrolled
    Russian Federation: 60
    Country: Number of subjects enrolled
    South Africa: 11
    Country: Number of subjects enrolled
    Sweden: 6
    Country: Number of subjects enrolled
    Thailand: 9
    Country: Number of subjects enrolled
    United States: 40
    Worldwide total number of subjects
    376
    EEA total number of subjects
    149
    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)
    252
    From 65 to 84 years
    119
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled in 90 centers across 23 countries.

    Pre-assignment
    Screening details
    		 A total of 558 subjects were screened of which 376 participants were randomized on a 1:1 basis.

    Period 1
    Period 1 title
    Treatment period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ribociclib 400 mg
    Arm description
    		 Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ribociclib
    Investigational medicinal product code
    Other name
    LEE011
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

    Investigational medicinal product name
    Goserelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

    Investigational medicinal product name
    Letrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Letrozole 2.5 mg tablets for oral use QD continuously

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Anastrozole 1 mg tablets for oral use QD continuously

    Arm title
    		 Ribociclib 600 mg
    Arm description
    		 Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ribociclib
    Investigational medicinal product code
    Other name
    LEE011
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

    Investigational medicinal product name
    Letrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Letrozole 2.5 mg tablets for oral use QD continuously

    Investigational medicinal product name
    Goserelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Anastrozole 1 mg tablets for oral use QD continuously

    Number of subjects in period 1
    		Ribociclib 400 mg Ribociclib 600 mg
    Started
    188
    188
    Completed
    0
    0
    Not completed
    188
    188
         Adverse event, serious fatal
    2
    3
         Consent withdrawn by subject
    9
    5
         Physician decision
    9
    7
         Adverse event, non-fatal
    21
    24
         Lost to follow-up
    1
    1
         Progressive disease
    98
    94
         Sponsor decision
    46
    53
         Protocol deviation
    2
    1
    Period 2
    Period 2 title
    Post-treatment efficacy follow-up
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Ribociclib 400 mg
    Arm description
    		 Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ribociclib
    Investigational medicinal product code
    Other name
    LEE011
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

    Investigational medicinal product name
    Goserelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

    Investigational medicinal product name
    Letrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Letrozole 2.5 mg tablets for oral use QD continuously

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Anastrozole 1 mg tablets for oral use QD continuously

    Arm title
    		 Ribociclib 600 mg
    Arm description
    		 Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ribociclib
    Investigational medicinal product code
    Other name
    LEE011
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

    Investigational medicinal product name
    Goserelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

    Investigational medicinal product name
    Letrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Letrozole 2.5 mg tablets for oral use QD continuously

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Anastrozole 1 mg tablets for oral use QD continuously

    Number of subjects in period 2
    		Ribociclib 400 mg Ribociclib 600 mg
    Started
    22
    26
    Completed
    0
    0
    Not completed
    22
    26
         Adverse event, serious fatal
    1
    -
         Consent withdrawn by subject
    4
    3
         Physician decision
    1
    2
         Adverse event, non-fatal
    1
    -
         Lost to follow-up
    1
    -
         Progressive disease
    11
    14
         Sponsor decision
    3
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ribociclib 400 mg
    Reporting group description
    		 Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)

    Reporting group title
    Ribociclib 600 mg
    Reporting group description
    		 Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)

    Reporting group values
    		 Ribociclib 400 mg Ribociclib 600 mg Total
    Number of subjects
    		 188 188 376
    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)
    		 124 128 252
        From 65-84 years
    		 59 60 119
        85 years and over
    		 5 0 5
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 58.7 ( 12.96 ) 57.0 ( 12.37 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 188 188 376
        Male
    		 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 147 143 290
        Native American or Alaska Native
    		 14 10 24
        Asian
    		 13 9 22
        Black
    		 5 12 17
        Other
    		 1 4 5
        Unknown
    		 8 10 18

    End points

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    End points reporting groups
    Reporting group title
    Ribociclib 400 mg
    Reporting group description
    		 Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)

    Reporting group title
    Ribociclib 600 mg
    Reporting group description
    		 Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
    Reporting group title
    Ribociclib 400 mg
    Reporting group description
    		 Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)

    Reporting group title
    Ribociclib 600 mg
    Reporting group description
    		 Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)

    Primary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR) [1]
    End point description
    ORR defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by local investigators according to RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
    End point type
    Primary
    End point timeframe
    Up to 23.8 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics performed
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    188
    188
    Units: Percentage of participants
        number (confidence interval 95%)
    41.5 (34.4 to 48.7)
    45.3 (38.1 to 52.6)
    No statistical analyses for this end point

    Secondary: Change from baseline in QTc (with Fridericia's correction) at Cycle 1 Day 15 (at 2 hours post-dose)

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    End point title
    		 Change from baseline in QTc (with Fridericia's correction) at Cycle 1 Day 15 (at 2 hours post-dose)
    End point description
    Electrocardiogram (ECG) data was collected via 12-lead digital ECG machines. Change from baseline in the QT interval (a segment of the ECG that reflects the time it takes for the heart to repolarize after each heartbeat) was corrected for heart rate using Fridericia's formula (ΔQTcF).
    End point type
    Secondary
    End point timeframe
    Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    174
    175
    Units: milliseconds
        arithmetic mean (standard deviation)
    12.5 ( 12.91 )
    19.7 ( 18.50 )
    No statistical analyses for this end point

    Secondary: Clinical benefit rate (CBR)

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    End point title
    		 Clinical benefit rate (CBR)
    End point description
    Clinical benefit rate (CBR) was defined as the proportion of patients with a best overall response of complete response (CR), or partial response (PR), or an overall response of stable disease (SD), lasting for at least 24 weeks. CR, PR, and SD were defined as per local review as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1. A patient was considered to have SD for 24 weeks or longer if a SD response was recorded at 24-1=23 weeks or later from randomization, allowing for the ±1 week visit window for tumor assessments. CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
    End point type
    Secondary
    End point timeframe
    Up to approximately 60 months
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    188
    188
    Units: Participants
    142
    133
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS)

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    End point title
    		 Progression-free survival (PFS)
    End point description
    Progression free survival (PFS) was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. PFS was censored if no PFS event was observed. The censoring date was the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression. PFS was assessed via a local radiology assessment as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1.
    End point type
    Secondary
    End point timeframe
    Up to approximately 60 months
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    188
    188
    Units: Months
        median (full range (min-max))
    26.9 (20.3 to 30.4)
    25.1 (19.4 to 33.4)
    No statistical analyses for this end point

    Secondary: Duration of response (DOR)

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    End point title
    		 Duration of response (DOR)
    End point description
    Duration of response (DOR) only applied to patients whose best overall response was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progression or death due to underlying cancer. Patients continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
    End point type
    Secondary
    End point timeframe
    Up to approximately 60 months
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    90
    103
    Units: Months
        median (confidence interval 95%)
    26.5 (16.8 to 999)
    28.8 (22.6 to 999)
    No statistical analyses for this end point

    Secondary: Time to response (TTR)

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    End point title
    		 Time to response (TTR)
    End point description
    Time to response (TTR) was defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which had to be subsequently confirmed (although the date of initial response was used, not the date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
    End point type
    Secondary
    End point timeframe
    Up to approximately 60 months
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    90
    103
    Units: Months
        median (confidence interval 95%)
    13.1 (7.4 to 999)
    9.0 (5.6 to 16.4)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK) of ribociclib: Maximum observed plasma concentration (Cmax)

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    End point title
    		 Pharmacokinetics (PK) of ribociclib: Maximum observed plasma concentration (Cmax)
    End point description
    PK parameters were calculated by non-compartmental analysis. Cmax is the maximum observed plasma drug concentration after single dose administration.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    20
    16
    Units: nanogram / milliliter (ng / mL)
        arithmetic mean (standard deviation)
    1240 ( 739 )
    1740 ( 918 )
    No statistical analyses for this end point

    Secondary: PK of ribociclib: Time to reach observed maximum concentration (Tmax)

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    End point title
    		 PK of ribociclib: Time to reach observed maximum concentration (Tmax)
    End point description
    PK parameters were calculated by non-compartmental analysis. Tmax is the time to reach maximum observed plasma concentration. Actual recorded sampling times were considered for the calculations.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    20
    16
    Units: hours (h)
        median (full range (min-max))
    2.08 (1.83 to 4.38)
    4.00 (1.83 to 23.8)
    No statistical analyses for this end point

    Secondary: PK of ribociclib: Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24)

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    End point title
    		 PK of ribociclib: Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24)
    End point description
    PK parameters were calculated by non-compartmental analysis. AUC0-24 is the area under the plasma concentration-time curve from 0 to 24 hours
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
    End point values
    		 Ribociclib 400 mg Ribociclib 600 mg
    Number of subjects analysed
    17
    13
    Units: ng x h / mL
        arithmetic mean (standard deviation)
    18700 ( 11600 )
    31600 ( 14300 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were collected from first dose of study treatment to 30 days after last dose of study medication (on-treatment), up to 23.8 months.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Ribociclib 600mg
    Reporting group description
    		 Ribociclib 600mg

    Reporting group title
    Ribociclib 400mg
    Reporting group description
    		 Ribociclib 400mg

    Serious adverse events
    		 Ribociclib 600mg Ribociclib 400mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    37 / 188 (19.68%)
    38 / 188 (20.21%)
         number of deaths (all causes)
    6
    5
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (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 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Peripheral embolism
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Ill-defined disorder
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dyspnoea
         subjects affected / exposed
    4 / 188 (2.13%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 188 (1.06%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary thrombosis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 188 (0.00%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation injury
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 188 (1.06%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Hydrocephalus
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         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 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         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
    Neutropenia
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 188 (0.00%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 188 (0.00%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 188 (0.53%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         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 impairment
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    2 / 188 (1.06%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fracture pain
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 188 (1.06%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (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
    Pneumonia
         subjects affected / exposed
    3 / 188 (1.60%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 188 (0.53%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    2 / 188 (1.06%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronavirus pneumonia
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 188 (0.53%)
    3 / 188 (1.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 188 (1.06%)
    2 / 188 (1.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sepsis
         subjects affected / exposed
    1 / 188 (0.53%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 188 (0.00%)
    1 / 188 (0.53%)
         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 / 188 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ribociclib 600mg Ribociclib 400mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    178 / 188 (94.68%)
    175 / 188 (93.09%)
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    40 / 188 (21.28%)
    41 / 188 (21.81%)
         occurrences all number
    52
    57
    Alanine aminotransferase increased
         subjects affected / exposed
    47 / 188 (25.00%)
    49 / 188 (26.06%)
         occurrences all number
    55
    63
    Blood alkaline phosphatase increased
         subjects affected / exposed
    17 / 188 (9.04%)
    11 / 188 (5.85%)
         occurrences all number
    22
    17
    Blood creatinine increased
         subjects affected / exposed
    15 / 188 (7.98%)
    12 / 188 (6.38%)
         occurrences all number
    23
    13
    White blood cell count decreased
         subjects affected / exposed
    22 / 188 (11.70%)
    13 / 188 (6.91%)
         occurrences all number
    31
    23
    Weight decreased
         subjects affected / exposed
    11 / 188 (5.85%)
    11 / 188 (5.85%)
         occurrences all number
    11
    11
    Neutrophil count decreased
         subjects affected / exposed
    24 / 188 (12.77%)
    25 / 188 (13.30%)
         occurrences all number
    69
    60
    Lipase increased
         subjects affected / exposed
    12 / 188 (6.38%)
    9 / 188 (4.79%)
         occurrences all number
    16
    12
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    16 / 188 (8.51%)
    17 / 188 (9.04%)
         occurrences all number
    17
    22
    Electrocardiogram QT prolonged
         subjects affected / exposed
    26 / 188 (13.83%)
    14 / 188 (7.45%)
         occurrences all number
    49
    17
    Vascular disorders
    Hot flush
         subjects affected / exposed
    14 / 188 (7.45%)
    24 / 188 (12.77%)
         occurrences all number
    14
    24
    Hypertension
         subjects affected / exposed
    10 / 188 (5.32%)
    6 / 188 (3.19%)
         occurrences all number
    15
    8
    Nervous system disorders
    Headache
         subjects affected / exposed
    31 / 188 (16.49%)
    18 / 188 (9.57%)
         occurrences all number
    65
    20
    Blood and lymphatic system disorders
    Lymphopenia
         subjects affected / exposed
    18 / 188 (9.57%)
    17 / 188 (9.04%)
         occurrences all number
    34
    27
    Leukopenia
         subjects affected / exposed
    52 / 188 (27.66%)
    40 / 188 (21.28%)
         occurrences all number
    124
    94
    Anaemia
         subjects affected / exposed
    49 / 188 (26.06%)
    31 / 188 (16.49%)
         occurrences all number
    67
    47
    Neutropenia
         subjects affected / exposed
    125 / 188 (66.49%)
    100 / 188 (53.19%)
         occurrences all number
    414
    255
    Thrombocytopenia
         subjects affected / exposed
    19 / 188 (10.11%)
    13 / 188 (6.91%)
         occurrences all number
    37
    17
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    12 / 188 (6.38%)
    8 / 188 (4.26%)
         occurrences all number
    13
    8
    Fatigue
         subjects affected / exposed
    40 / 188 (21.28%)
    22 / 188 (11.70%)
         occurrences all number
    50
    23
    Asthenia
         subjects affected / exposed
    23 / 188 (12.23%)
    24 / 188 (12.77%)
         occurrences all number
    26
    26
    Pain
         subjects affected / exposed
    14 / 188 (7.45%)
    1 / 188 (0.53%)
         occurrences all number
    21
    1
    Pyrexia
         subjects affected / exposed
    12 / 188 (6.38%)
    11 / 188 (5.85%)
         occurrences all number
    14
    12
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    12 / 188 (6.38%)
    10 / 188 (5.32%)
         occurrences all number
    15
    18
    Abdominal pain upper
         subjects affected / exposed
    12 / 188 (6.38%)
    5 / 188 (2.66%)
         occurrences all number
    15
    6
    Nausea
         subjects affected / exposed
    44 / 188 (23.40%)
    31 / 188 (16.49%)
         occurrences all number
    63
    37
    Diarrhoea
         subjects affected / exposed
    25 / 188 (13.30%)
    22 / 188 (11.70%)
         occurrences all number
    35
    24
    Constipation
         subjects affected / exposed
    21 / 188 (11.17%)
    17 / 188 (9.04%)
         occurrences all number
    22
    20
    Vomiting
         subjects affected / exposed
    22 / 188 (11.70%)
    15 / 188 (7.98%)
         occurrences all number
    27
    16
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    15 / 188 (7.98%)
    8 / 188 (4.26%)
         occurrences all number
    17
    10
    Cough
         subjects affected / exposed
    23 / 188 (12.23%)
    17 / 188 (9.04%)
         occurrences all number
    26
    24
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    16 / 188 (8.51%)
    7 / 188 (3.72%)
         occurrences all number
    17
    9
    Pruritus
         subjects affected / exposed
    17 / 188 (9.04%)
    4 / 188 (2.13%)
         occurrences all number
    24
    4
    Dry skin
         subjects affected / exposed
    15 / 188 (7.98%)
    6 / 188 (3.19%)
         occurrences all number
    17
    6
    Alopecia
         subjects affected / exposed
    24 / 188 (12.77%)
    19 / 188 (10.11%)
         occurrences all number
    24
    20
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    28 / 188 (14.89%)
    31 / 188 (16.49%)
         occurrences all number
    32
    41
    Back pain
         subjects affected / exposed
    23 / 188 (12.23%)
    20 / 188 (10.64%)
         occurrences all number
    26
    27
    Pain in extremity
         subjects affected / exposed
    17 / 188 (9.04%)
    12 / 188 (6.38%)
         occurrences all number
    23
    13
    Infections and infestations
    COVID-19
         subjects affected / exposed
    27 / 188 (14.36%)
    17 / 188 (9.04%)
         occurrences all number
    27
    17
    Nasopharyngitis
         subjects affected / exposed
    12 / 188 (6.38%)
    6 / 188 (3.19%)
         occurrences all number
    14
    7
    Urinary tract infection
         subjects affected / exposed
    17 / 188 (9.04%)
    15 / 188 (7.98%)
         occurrences all number
    19
    21
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    12 / 188 (6.38%)
    9 / 188 (4.79%)
         occurrences all number
    15
    12
    Decreased appetite
         subjects affected / exposed
    13 / 188 (6.91%)
    11 / 188 (5.85%)
         occurrences all number
    14
    13
    Hypocalcaemia
         subjects affected / exposed
    15 / 188 (7.98%)
    12 / 188 (6.38%)
         occurrences all number
    23
    17
    Hypokalaemia
         subjects affected / exposed
    10 / 188 (5.32%)
    9 / 188 (4.79%)
         occurrences all number
    15
    10
    Hypophosphataemia
         subjects affected / exposed
    10 / 188 (5.32%)
    4 / 188 (2.13%)
         occurrences all number
    15
    5

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Jan 2020
    Key changes introduced in Amendment 1 for ribociclib: 1. ILD/pneumonitis observed with all CDK4/6 inhibitors; ribociclib dose adjustment and management guidance added. 2. TEN reported post-marketing (not in trials); guidance updated to discontinue ribociclib if diagnosed. 3. For patients on tamoxifen/toremifene: a. These drugs must be stopped for a 5 half-life washout before randomization due to QT risk. b. Postmenopausal status criteria updated per NCCN v4 2018. 4. Sodium and phosphorus level checks removed from inclusion criteria; concurrent HRT use added as exclusion. 5. Patients with prior treatment toxicities (not safety risks) now allowed. 6. Uncorrected hypocalcemia added as exclusion due to QT risk. 7. Corticosteroid use guidance aligned with ‘Concomitant medications’ section. 8. Hormonal contraceptives prohibited due to breast cancer risk. 9. Vasectomy as contraception requires medical confirmation (per CTFG). 10. Clarified eligibility for patients in other medical research. 11. Lists of prohibited and cautionary medications during treatment added. 12. Justification for PK analysis sample size included.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results.
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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
    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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