Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A randomised, phase II trial to evaluate a treatment with Tyrosine Kinase Inhibitor of Epidermal Growth Factor (EGFR-TKI) versus EGFR-TKI associated with an anti-estrogen treatment (fulvestrant) in women with an advanced stage of non squamous non small cell lung cancer

    Summary
    EudraCT number
    		 2011-003571-11
    Trial protocol
    		 FR  
    Global end of trial date
    30 Nov 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Feb 2023
    First version publication date
    02 Feb 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IFCT-1003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01556191
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    IFCT
    Sponsor organisation address
    10 rue de la Grange Batelière, Paris, France, 75009
    Public contact
    IFCT, IFCT, 33 156811045, contact@ifct.fr
    Scientific contact
    IFCT, IFCT, 33 156811045, contact@ifct.fr
    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
    01 May 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    3-months progression free survival for patient with EGFR mutation 9-months progression free survival for patient with EGFR wild type
    Protection of trial subjects
    Algorithms for management of adverse events were provided in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 May 2012
    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
    France: 379
    Worldwide total number of subjects
    379
    EEA total number of subjects
    379
    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)
    177
    From 65 to 84 years
    196
    85 years and over
    6

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 379 patients included. 204 patients (gefitinib 104 and G+Fulvestrant 100) and 175 patients (erlotinib 87 and E+Fulvestrant 88) were enrolled in the EGFR mutated and EGFR-WT cohorts respectively.

    Pre-assignment
    Screening details
    		 Main inclusion criteria were histologically confirmed inoperable stage III or stage IV nonsquamous NSCLCs, the presence of at least one lesion that could be measured by a CT scan (RECIST v1.1), postmenopausal female (either >60 year or amenorrhea >12 months), with a World Health Organization performance index of 0, 1, or 2.

    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
    		 A1 - EGFR mut Gefitinib
    Arm description
    		 EGFR mutated patients receiving Gefitinib.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefitinib
    Investigational medicinal product code
    Other name
    Iressa
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Gefitinib is administered orally in a 250 mg tablet (single dose) / day

    Arm title
    		 B1 - EGFR mut Gefitinib Fulvestrant
    Arm description
    		 EGFR mutated patients receiving Gefitinib + Fulvestrant
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefitinib
    Investigational medicinal product code
    Other name
    Iressa
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Gefitinib is administered orally in a 250 mg tablet (single dose) / day

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Prefilled syringe of 5 ml (250 mg of fulvestrant) : Two slow, intramuscular injections (2 x 250 mg) by month with an additional 500 mg dose two weeks after the initial dose. 5 ml in each buttock with prefilled syringes.

    Arm title
    		 A2 - EGFR WT Erlotinib
    Arm description
    		 EGFR WT patients receiving Erlotinib.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Tarceva
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Erlotinib is administered orally in a 150 mg tablet (also available in 25 and 100 mg), to be taken on an empty stomach (one hour before or two hours after eating) by day.

    Arm title
    		 B2 - EGFR WT Erlotinib Fulvestrant
    Arm description
    		 EGFR WT patients receiving Erlotinib + Fulvestrant
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Tarceva
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Erlotinib is administered orally in a 150 mg tablet (also available in 25 and 100 mg), to be taken on an empty stomach (one hour before or two hours after eating) by day.

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Prefilled syringe of 5 ml (250 mg of fulvestrant) : Two slow, intramuscular injections (2 x 250 mg) by month with an additional 500 mg dose two weeks after the initial dose. 5 ml in each buttock with prefilled syringes.

    Number of subjects in period 1
    		A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Started
    104
    100
    87
    88
    Completed
    9
    3
    1
    0
    Not completed
    95
    97
    86
    88
         Patient's choice
    1
    3
    2
    -
         Adverse event, non-fatal
    8
    9
    3
    2
         Death
    3
    3
    5
    4
         Other
    7
    5
    3
    4
         Intercurrent disease
    -
    -
    -
    1
         Complication
    -
    1
    -
    -
         Second cancer
    -
    1
    -
    -
         Lack of efficacy
    76
    75
    73
    77

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    A1 - EGFR mut Gefitinib
    Reporting group description
    		 EGFR mutated patients receiving Gefitinib.

    Reporting group title
    B1 - EGFR mut Gefitinib Fulvestrant
    Reporting group description
    		 EGFR mutated patients receiving Gefitinib + Fulvestrant

    Reporting group title
    A2 - EGFR WT Erlotinib
    Reporting group description
    		 EGFR WT patients receiving Erlotinib.

    Reporting group title
    B2 - EGFR WT Erlotinib Fulvestrant
    Reporting group description
    		 EGFR WT patients receiving Erlotinib + Fulvestrant

    Reporting group values
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant Total
    Number of subjects
    		 104 100 87 88 379
    Age categorical
    Age distribution
    Units: Subjects
        Adults (18-64 years)
    		 34 38 47 58 177
        From 65-84 years
    		 69 58 39 30 196
        85 years and over
    		 1 4 1 0 6
    Age continuous
    Units: years
        median (full range (min-max))
    		 67.71 (49.5 to 89.1) 68.30 (50.1 to 90.9) 64.56 (43.6 to 85.4) 61.03 (43.7 to 80.5) -
    Gender categorical
    Units: Subjects
        Female
    		 104 100 87 88 379
    Smoking population
    Number of smoking and non smoking patients
    Units: Subjects
        Smoker
    		 24 31 62 70 187
        Non smoker
    		 80 69 25 18 192
    ECOG Performance Status
    Patient's ECOG PS during the screening/inclusion visit.
    Units: Subjects
        ECOG 0
    		 42 42 27 41 152
        ECOG 1
    		 53 49 46 33 181
        ECOG 2
    		 9 9 14 14 46
    Histology subtype
    Histology subtype of patients' cancer
    Units: Subjects
        Adenocarcinoma
    		 99 95 82 82 358
        Non adenocarcinoma
    		 5 5 5 6 21
    EGFR mutation
    Patient with an EGFR mutation and patients with a WT EGFR gene.
    Units: Subjects
        EGFR WT
    		 0 0 85 88 173
        EGFR muted
    		 104 100 0 0 204
        MISSING
    		 2 2
    Previous line of treatment
    Number of patients' previous line of treatment.
    Units: Subjects
        1 previous line of treatment
    		 104 100 61 59 324
        2 or more previous lines of treatment
    		 0 0 26 29 55
    Menopausal status
    Menopausal status of the patients
    Units: Subjects
        Premenopausal patient
    		 0 0 0 0 0
        Postmenopausal patient
    		 104 100 87 88 379
    Estrogen Receptor Alpha (ERa)
    Results of the Estrogen Receptor Alpha positivity test
    Units: Subjects
        Negative
    		 34 41 26 25 126
        Positive
    		 10 9 7 8 34
        Unknown
    		 60 50 54 55 219
    Pack-years for smokers
    Number of pack-years for the smokers.
    Units: Pack-years
        median (full range (min-max))
    		 12 (1 to 54) 11.5 (1 to 50) 37.5 (1 to 92) 35 (1 to 120) -
    Subject analysis sets

    Subject analysis set title
    Intent-to-treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All patients who were included are counted into this subject analysis set

    Subject analysis sets values
    		 Intent-to-treat
    Number of subjects
    379
    Age categorical
    Age distribution
    Units: Subjects
        Adults (18-64 years)
    177
        From 65-84 years
    196
        85 years and over
    6
    Age continuous
    Units: years
        median (full range (min-max))
    66.18 (43.6 to 90.9)
    Gender categorical
    Units: Subjects
        Female
    379
    Smoking population
    Number of smoking and non smoking patients
    Units: Subjects
        Smoker
    187
        Non smoker
    192
    ECOG Performance Status
    Patient's ECOG PS during the screening/inclusion visit.
    Units: Subjects
        ECOG 0
    152
        ECOG 1
    181
        ECOG 2
    46
    Histology subtype
    Histology subtype of patients' cancer
    Units: Subjects
        Adenocarcinoma
    358
        Non adenocarcinoma
    21
    EGFR mutation
    Patient with an EGFR mutation and patients with a WT EGFR gene.
    Units: Subjects
        EGFR WT
    173
        EGFR muted
    204
        MISSING
    2
    Previous line of treatment
    Number of patients' previous line of treatment.
    Units: Subjects
        1 previous line of treatment
    324
        2 or more previous lines of treatment
    55
    Menopausal status
    Menopausal status of the patients
    Units: Subjects
        Premenopausal patient
    0
        Postmenopausal patient
    379
    Estrogen Receptor Alpha (ERa)
    Results of the Estrogen Receptor Alpha positivity test
    Units: Subjects
        Negative
    126
        Positive
    34
        Unknown
    219
    Pack-years for smokers
    Number of pack-years for the smokers.
    Units: Pack-years
        median (full range (min-max))
    29 (1 to 120)

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    A1 - EGFR mut Gefitinib
    Reporting group description
    		 EGFR mutated patients receiving Gefitinib.

    Reporting group title
    B1 - EGFR mut Gefitinib Fulvestrant
    Reporting group description
    		 EGFR mutated patients receiving Gefitinib + Fulvestrant

    Reporting group title
    A2 - EGFR WT Erlotinib
    Reporting group description
    		 EGFR WT patients receiving Erlotinib.

    Reporting group title
    B2 - EGFR WT Erlotinib Fulvestrant
    Reporting group description
    		 EGFR WT patients receiving Erlotinib + Fulvestrant

    Subject analysis set title
    Intent-to-treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All patients who were included are counted into this subject analysis set

    Primary: Progression free survival at 9 months

    		 Close Top of page
    End point title
    		 Progression free survival at 9 months [1]
    End point description
    Progression free survival (PFS) at 9 months for EGFR mutated patients. PFS : The length of time between randomisation and tumour progression or death (any cause).
    End point type
    Primary
    End point timeframe
    From inclusion to 9 months post inclusion.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point : Progression free survival at 9 month is specific to 2 arms (A1 and B1).
    End point values
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant
    Number of subjects analysed
    93 [2]
    93 [3]
    Units: Patients
        Number of patient without progression at 9 months
    50
    54
    Notes
    [2] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    [3] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    Statistical analysis title
    		 Progression free survival at 9 month
    Statistical analysis description
    EGFR mutated patients: The statistical hypotheses in mutated patients are as follows: H0: p0 (9-month progression-free survival rate) ≤ 45% H1: p1 (9-month progression-free survival rate) ≥ 60% Under these assumptions, 102 patients (93 + 10% non-evaluable) are needed in each arm, i.e. 204 patients.
    Comparison groups
    A1 - EGFR mut Gefitinib v B1 - EGFR mut Gefitinib Fulvestrant
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.05
    Method
    		 Binomial test
    Parameter type
    		 Difference of proportion
    Confidence interval
    Notes
    [4] - No comment

    Primary: Progression free survival at 3 months

    		 Close Top of page
    End point title
    		 Progression free survival at 3 months [5]
    End point description
    Progression free survival at 3 months for EGFR wild type patients. PFS : The length of time between randomisation and tumour progression or death (any cause).
    End point type
    Primary
    End point timeframe
    From inclusion to 3 months post inclusion
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point : Progression free survival at 9 month is specific to 2 arms (A2 and B2).
    End point values
    		 A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Number of subjects analysed
    83 [6]
    86 [7]
    Units: Patients
        Number of patients without progression at 3 months
    29
    29
    Notes
    [6] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    [7] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    Statistical analysis title
    		 Progression free survival at 3 month
    Statistical analysis description
    EGFR-unmutated patients : The statistical hypotheses in non-mutated patients are as follows: H0: p0 (Progression-free survival rate at 3 months) ≤ 30% H1: p1 (3-month progression-free survival rate) ≥ 45% Under these assumptions, 95 patients (86 + 10% non-evaluable) are needed in each arm, i.e. 190 patients.
    Comparison groups
    A2 - EGFR WT Erlotinib v B2 - EGFR WT Erlotinib Fulvestrant
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.05
    Method
    		 Binomial test
    Parameter type
    		 Difference of proportion
    Confidence interval
    Notes
    [8] - No comment

    Secondary: Response at 2 months at intent to treat population

    		 Close Top of page
    End point title
    		 Response at 2 months at intent to treat population
    End point description
    Response at 2 months at intent to treat population
    End point type
    Secondary
    End point timeframe
    From inclusion to 2 months post inclusion
    End point values
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Number of subjects analysed
    104
    100
    87
    88
    Units: Patients
        Complete response
    1
    0
    0
    0
        Partial response
    56
    52
    3
    2
        Stable disease
    35
    34
    25
    24
        Disease progression
    12
    14
    59
    62
    No statistical analyses for this end point

    Secondary: Best response in intent to treat population

    		 Close Top of page
    End point title
    		 Best response in intent to treat population
    End point description
    Best response in intent to treat population
    End point type
    Secondary
    End point timeframe
    From inclusion to the end of treatment
    End point values
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Number of subjects analysed
    104
    100
    87
    88
    Units: Patients
        Complete response
    1
    2
    1
    0
        Partial response
    71
    62
    3
    3
        Stable disease
    23
    23
    26
    24
        Disease progression
    9
    13
    57
    61
    No statistical analyses for this end point

    Secondary: Progression free survival

    		 Close Top of page
    End point title
    		 Progression free survival
    End point description
    Progression free survival. PFS : The length of time between randomisation and tumour progression or death (any cause).
    End point type
    Secondary
    End point timeframe
    From inclusion to the first observed progression (RECIST 1.1)
    End point values
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Number of subjects analysed
    93 [9]
    93 [10]
    83 [11]
    86 [12]
    Units: month
    median (confidence interval 95%)
        PFS
    9.4 (8.0 to 12.7)
    9.9 (7.7 to 11.2)
    2.0 (1.8 to 2.6)
    1.8 (1.7 to 2.1)
    Notes
    [9] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    [10] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    [11] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    [12] - Intent to treat patients restricted to the number of necessary subjects calculated in the protocole
    No statistical analyses for this end point

    Secondary: Overall survival

    		 Close Top of page
    End point title
    		 Overall survival
    End point description
    Overall survival (in months)
    End point type
    Secondary
    End point timeframe
    From inclusion to death.
    End point values
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Number of subjects analysed
    104
    98
    83
    88
    Units: month
    median (confidence interval 95%)
        Overall survival in months
    29.9 (23.2 to 43.8)
    22.1 (18.6 to 25.7)
    7.3 (5.4 to 9.3)
    10.0 (6.6 to 14.6)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse event monitoring was performed at day 15 of the first cycle, before each cycle (i.e., every 4 weeks until the end of protocol treatment), and for 30 days after drug discontinuation for each patient
    Adverse event reporting additional description
    The maximal grade of adverse events was collected by cycle of treatment.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21
    Reporting groups
    Reporting group title
    A1 - EGFR mut Gefitinib
    Reporting group description
    		 Patients with an EGFR mutation who received gefitinib only

    Reporting group title
    B1 - EGFR mut Gefitinib Fulvestrant
    Reporting group description
    		 Patients with an EGFR mutation who received gefitinib anf fulvestrant

    Reporting group title
    A2 - EGFR WT Erlotinib
    Reporting group description
    		 Patients with a WT EGFR who received erlotinib only

    Reporting group title
    B2 - EGFR WT Erlotinib Fulvestrant
    Reporting group description
    		 Patients with a WT EGFR who received erlotinib and fulvestrant

    Serious adverse events
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Total subjects affected by serious adverse events
         subjects affected / exposed
    33 / 103 (32.04%)
    26 / 99 (26.26%)
    46 / 87 (52.87%)
    33 / 88 (37.50%)
         number of deaths (all causes)
    3
    3
    7
    4
         number of deaths resulting from adverse events
    0
    1
    5
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bronchial carcinoma
         subjects affected / exposed
    0 / 103 (0.00%)
    2 / 99 (2.02%)
    5 / 87 (5.75%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 1
    Colon cancer stage 0
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pericarditis malignant
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Second primary malignancy
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis superficial
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    5 / 103 (4.85%)
    2 / 99 (2.02%)
    3 / 87 (3.45%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    2 / 87 (2.30%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    4 / 103 (3.88%)
    5 / 99 (5.05%)
    16 / 87 (18.39%)
    12 / 88 (13.64%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 6
    2 / 17
    1 / 13
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 12
    0 / 7
    Inflammation
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device pain
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 103 (2.91%)
    1 / 99 (1.01%)
    4 / 87 (4.60%)
    5 / 88 (5.68%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Haemoptysis
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    2 / 87 (2.30%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 99 (1.01%)
    1 / 87 (1.15%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 99 (1.01%)
    2 / 87 (2.30%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 103 (0.00%)
    2 / 99 (2.02%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Weight decreased
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accident at home
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Fall
         subjects affected / exposed
    4 / 103 (3.88%)
    1 / 99 (1.01%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pericardial effusion
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    2 / 103 (1.94%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 103 (0.00%)
    2 / 99 (2.02%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Cognitive disorder
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Hypoaesthesia oral
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokinesia
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    IIIrd nerve disorder
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    1 / 103 (0.97%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Neuralgia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Visual acuity reduced
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 103 (1.94%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Dysphagia
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal obstruction
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    1 / 87 (1.15%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Proctitis
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    5 / 88 (5.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    2 / 87 (2.30%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subacute cutaneous lupus erythematosus
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    2 / 87 (2.30%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    2 / 87 (2.30%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    2 / 103 (1.94%)
    2 / 99 (2.02%)
    3 / 87 (3.45%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    2 / 87 (2.30%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes simplex
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 103 (0.00%)
    1 / 99 (1.01%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal infection
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cell death
         subjects affected / exposed
    0 / 103 (0.00%)
    0 / 99 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 103 (0.00%)
    2 / 99 (2.02%)
    2 / 87 (2.30%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 A1 - EGFR mut Gefitinib B1 - EGFR mut Gefitinib Fulvestrant A2 - EGFR WT Erlotinib B2 - EGFR WT Erlotinib Fulvestrant
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    101 / 103 (98.06%)
    99 / 99 (100.00%)
    87 / 87 (100.00%)
    86 / 88 (97.73%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    3 / 103 (2.91%)
    11 / 99 (11.11%)
    0 / 87 (0.00%)
    7 / 88 (7.95%)
         occurrences all number
    12
    56
    0
    11
    Epistaxis
         subjects affected / exposed
    7 / 103 (6.80%)
    7 / 99 (7.07%)
    2 / 87 (2.30%)
    4 / 88 (4.55%)
         occurrences all number
    12
    9
    3
    5
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    45 / 103 (43.69%)
    56 / 99 (56.57%)
    34 / 87 (39.08%)
    25 / 88 (28.41%)
         occurrences all number
    117
    131
    82
    41
    Chest pain
         subjects affected / exposed
    16 / 103 (15.53%)
    12 / 99 (12.12%)
    10 / 87 (11.49%)
    10 / 88 (11.36%)
         occurrences all number
    48
    28
    18
    13
    General physical health deterioration
         subjects affected / exposed
    7 / 103 (6.80%)
    9 / 99 (9.09%)
    19 / 87 (21.84%)
    13 / 88 (14.77%)
         occurrences all number
    8
    10
    25
    15
    Fatigue
         subjects affected / exposed
    7 / 103 (6.80%)
    11 / 99 (11.11%)
    13 / 87 (14.94%)
    4 / 88 (4.55%)
         occurrences all number
    12
    25
    18
    4
    Oedema peripheral
         subjects affected / exposed
    8 / 103 (7.77%)
    10 / 99 (10.10%)
    7 / 87 (8.05%)
    2 / 88 (2.27%)
         occurrences all number
    13
    27
    7
    4
    Xerosis
         subjects affected / exposed
    11 / 103 (10.68%)
    6 / 99 (6.06%)
    2 / 87 (2.30%)
    3 / 88 (3.41%)
         occurrences all number
    20
    26
    3
    6
    Pain
         subjects affected / exposed
    4 / 103 (3.88%)
    5 / 99 (5.05%)
    6 / 87 (6.90%)
    4 / 88 (4.55%)
         occurrences all number
    6
    10
    7
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    32 / 103 (31.07%)
    33 / 99 (33.33%)
    20 / 87 (22.99%)
    28 / 88 (31.82%)
         occurrences all number
    109
    74
    42
    44
    Dyspnoea
         subjects affected / exposed
    34 / 103 (33.01%)
    25 / 99 (25.25%)
    27 / 87 (31.03%)
    23 / 88 (26.14%)
         occurrences all number
    88
    77
    57
    36
    Chest pain
         subjects affected / exposed
    12 / 103 (11.65%)
    10 / 99 (10.10%)
    3 / 87 (3.45%)
    1 / 88 (1.14%)
         occurrences all number
    24
    13
    3
    1
    Productive cough
         subjects affected / exposed
    6 / 103 (5.83%)
    2 / 99 (2.02%)
    4 / 87 (4.60%)
    2 / 88 (2.27%)
         occurrences all number
    10
    3
    4
    2
    Psychiatric disorders
    Depression
         subjects affected / exposed
    6 / 103 (5.83%)
    6 / 99 (6.06%)
    1 / 87 (1.15%)
    2 / 88 (2.27%)
         occurrences all number
    21
    7
    1
    3
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    35 / 103 (33.98%)
    29 / 99 (29.29%)
    7 / 87 (8.05%)
    9 / 88 (10.23%)
         occurrences all number
    115
    104
    12
    11
    Aspartate aminotransferase increased
         subjects affected / exposed
    29 / 103 (28.16%)
    25 / 99 (25.25%)
    9 / 87 (10.34%)
    12 / 88 (13.64%)
         occurrences all number
    110
    102
    18
    19
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    13 / 103 (12.62%)
    15 / 99 (15.15%)
    10 / 87 (11.49%)
    14 / 88 (15.91%)
         occurrences all number
    45
    49
    18
    20
    Weight decreased
         subjects affected / exposed
    7 / 103 (6.80%)
    14 / 99 (14.14%)
    17 / 87 (19.54%)
    7 / 88 (7.95%)
         occurrences all number
    16
    18
    21
    7
    Blood alkaline phosphatase increased
         subjects affected / exposed
    15 / 103 (14.56%)
    10 / 99 (10.10%)
    6 / 87 (6.90%)
    12 / 88 (13.64%)
         occurrences all number
    42
    23
    10
    17
    Nervous system disorders
    Headache
         subjects affected / exposed
    14 / 103 (13.59%)
    7 / 99 (7.07%)
    4 / 87 (4.60%)
    5 / 88 (5.68%)
         occurrences all number
    26
    17
    9
    5
    Paraesthesia
         subjects affected / exposed
    6 / 103 (5.83%)
    7 / 99 (7.07%)
    3 / 87 (3.45%)
    2 / 88 (2.27%)
         occurrences all number
    15
    9
    38
    2
    Dysgeusia
         subjects affected / exposed
    3 / 103 (2.91%)
    6 / 99 (6.06%)
    2 / 87 (2.30%)
    1 / 88 (1.14%)
         occurrences all number
    3
    7
    3
    1
    Confusional state
         subjects affected / exposed
    0 / 103 (0.00%)
    5 / 99 (5.05%)
    0 / 87 (0.00%)
    2 / 88 (2.27%)
         occurrences all number
    0
    6
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 103 (13.59%)
    20 / 99 (20.20%)
    31 / 87 (35.63%)
    29 / 88 (32.95%)
         occurrences all number
    62
    51
    50
    48
    Neutropenia
         subjects affected / exposed
    8 / 103 (7.77%)
    4 / 99 (4.04%)
    3 / 87 (3.45%)
    6 / 88 (6.82%)
         occurrences all number
    44
    14
    3
    16
    Thrombocytopenia
         subjects affected / exposed
    4 / 103 (3.88%)
    4 / 99 (4.04%)
    6 / 87 (6.90%)
    7 / 88 (7.95%)
         occurrences all number
    6
    18
    8
    14
    Lymphopenia
         subjects affected / exposed
    5 / 103 (4.85%)
    4 / 99 (4.04%)
    6 / 87 (6.90%)
    4 / 88 (4.55%)
         occurrences all number
    13
    8
    10
    8
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    7 / 103 (6.80%)
    9 / 99 (9.09%)
    3 / 87 (3.45%)
    1 / 88 (1.14%)
         occurrences all number
    13
    14
    3
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    8 / 103 (7.77%)
    7 / 99 (7.07%)
    8 / 87 (9.20%)
    2 / 88 (2.27%)
         occurrences all number
    18
    16
    10
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    66 / 103 (64.08%)
    60 / 99 (60.61%)
    42 / 87 (48.28%)
    42 / 88 (47.73%)
         occurrences all number
    338
    287
    95
    101
    Nausea
         subjects affected / exposed
    21 / 103 (20.39%)
    25 / 99 (25.25%)
    24 / 87 (27.59%)
    23 / 88 (26.14%)
         occurrences all number
    41
    62
    34
    32
    Vomiting
         subjects affected / exposed
    14 / 103 (13.59%)
    10 / 99 (10.10%)
    17 / 87 (19.54%)
    17 / 88 (19.32%)
         occurrences all number
    19
    12
    20
    20
    Constipation
         subjects affected / exposed
    17 / 103 (16.50%)
    13 / 99 (13.13%)
    6 / 87 (6.90%)
    9 / 88 (10.23%)
         occurrences all number
    34
    25
    6
    13
    Stomatitis
         subjects affected / exposed
    12 / 103 (11.65%)
    6 / 99 (6.06%)
    10 / 87 (11.49%)
    4 / 88 (4.55%)
         occurrences all number
    18
    11
    16
    6
    Abdominal pain
         subjects affected / exposed
    12 / 103 (11.65%)
    8 / 99 (8.08%)
    6 / 87 (6.90%)
    4 / 88 (4.55%)
         occurrences all number
    17
    11
    8
    4
    Abdominal pain upper
         subjects affected / exposed
    12 / 103 (11.65%)
    10 / 99 (10.10%)
    3 / 87 (3.45%)
    2 / 88 (2.27%)
         occurrences all number
    17
    19
    3
    3
    Dry mouth
         subjects affected / exposed
    6 / 103 (5.83%)
    10 / 99 (10.10%)
    5 / 87 (5.75%)
    2 / 88 (2.27%)
         occurrences all number
    6
    12
    6
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    9 / 103 (8.74%)
    4 / 99 (4.04%)
    1 / 87 (1.15%)
    3 / 88 (3.41%)
         occurrences all number
    25
    10
    2
    7
    Aphthous stomatitis
         subjects affected / exposed
    6 / 103 (5.83%)
    2 / 99 (2.02%)
    1 / 87 (1.15%)
    1 / 88 (1.14%)
         occurrences all number
    13
    3
    1
    1
    Pyrexia
         subjects affected / exposed
    10 / 103 (9.71%)
    3 / 99 (3.03%)
    1 / 87 (1.15%)
    5 / 88 (5.68%)
         occurrences all number
    11
    3
    1
    6
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    50 / 103 (48.54%)
    43 / 99 (43.43%)
    18 / 87 (20.69%)
    22 / 88 (25.00%)
         occurrences all number
    221
    158
    54
    42
    Rash
         subjects affected / exposed
    36 / 103 (34.95%)
    31 / 99 (31.31%)
    20 / 87 (22.99%)
    28 / 88 (31.82%)
         occurrences all number
    99
    91
    37
    64
    Acne
         subjects affected / exposed
    11 / 103 (10.68%)
    13 / 99 (13.13%)
    15 / 87 (17.24%)
    7 / 88 (7.95%)
         occurrences all number
    30
    34
    25
    13
    Erythema
         subjects affected / exposed
    18 / 103 (17.48%)
    16 / 99 (16.16%)
    5 / 87 (5.75%)
    6 / 88 (6.82%)
         occurrences all number
    33
    30
    13
    8
    Pruritus
         subjects affected / exposed
    17 / 103 (16.50%)
    14 / 99 (14.14%)
    7 / 87 (8.05%)
    5 / 88 (5.68%)
         occurrences all number
    35
    30
    8
    5
    Skin fissures
         subjects affected / exposed
    10 / 103 (9.71%)
    10 / 99 (10.10%)
    4 / 87 (4.60%)
    5 / 88 (5.68%)
         occurrences all number
    43
    17
    10
    13
    Skin toxicity
         subjects affected / exposed
    12 / 103 (11.65%)
    6 / 99 (6.06%)
    4 / 87 (4.60%)
    6 / 88 (6.82%)
         occurrences all number
    23
    9
    5
    6
    Nail disorder
         subjects affected / exposed
    14 / 103 (13.59%)
    8 / 99 (8.08%)
    1 / 87 (1.15%)
    2 / 88 (2.27%)
         occurrences all number
    27
    16
    3
    2
    Alopecia
         subjects affected / exposed
    9 / 103 (8.74%)
    11 / 99 (11.11%)
    1 / 87 (1.15%)
    1 / 88 (1.14%)
         occurrences all number
    17
    29
    2
    1
    Dermatitis acneiform
         subjects affected / exposed
    5 / 103 (4.85%)
    5 / 99 (5.05%)
    5 / 87 (5.75%)
    2 / 88 (2.27%)
         occurrences all number
    11
    7
    27
    4
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    10 / 103 (9.71%)
    7 / 99 (7.07%)
    12 / 87 (13.79%)
    8 / 88 (9.09%)
         occurrences all number
    35
    32
    46
    13
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    21 / 103 (20.39%)
    17 / 99 (17.17%)
    9 / 87 (10.34%)
    7 / 88 (7.95%)
         occurrences all number
    57
    42
    15
    13
    Arthralgia
         subjects affected / exposed
    12 / 103 (11.65%)
    18 / 99 (18.18%)
    8 / 87 (9.20%)
    5 / 88 (5.68%)
         occurrences all number
    20
    38
    11
    6
    Bone pain
         subjects affected / exposed
    9 / 103 (8.74%)
    10 / 99 (10.10%)
    8 / 87 (9.20%)
    10 / 88 (11.36%)
         occurrences all number
    18
    17
    19
    18
    Musculoskeletal pain
         subjects affected / exposed
    5 / 103 (4.85%)
    9 / 99 (9.09%)
    5 / 87 (5.75%)
    7 / 88 (7.95%)
         occurrences all number
    7
    13
    5
    7
    Muscle spasms
         subjects affected / exposed
    11 / 103 (10.68%)
    9 / 99 (9.09%)
    2 / 87 (2.30%)
    1 / 88 (1.14%)
         occurrences all number
    28
    40
    7
    2
    Pain in extremity
         subjects affected / exposed
    7 / 103 (6.80%)
    7 / 99 (7.07%)
    1 / 87 (1.15%)
    5 / 88 (5.68%)
         occurrences all number
    10
    13
    2
    9
    Myalgia
         subjects affected / exposed
    6 / 103 (5.83%)
    3 / 99 (3.03%)
    3 / 87 (3.45%)
    0 / 88 (0.00%)
         occurrences all number
    6
    4
    4
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 103 (0.97%)
    6 / 99 (6.06%)
    0 / 87 (0.00%)
    2 / 88 (2.27%)
         occurrences all number
    1
    7
    0
    2
    Infections and infestations
    Folliculitis
         subjects affected / exposed
    10 / 103 (9.71%)
    12 / 99 (12.12%)
    8 / 87 (9.20%)
    4 / 88 (4.55%)
         occurrences all number
    61
    40
    18
    5
    Paronychia
         subjects affected / exposed
    15 / 103 (14.56%)
    10 / 99 (10.10%)
    3 / 87 (3.45%)
    3 / 88 (3.41%)
         occurrences all number
    45
    26
    17
    6
    Bronchitis
         subjects affected / exposed
    8 / 103 (7.77%)
    8 / 99 (8.08%)
    5 / 87 (5.75%)
    3 / 88 (3.41%)
         occurrences all number
    15
    9
    6
    3
    Urinary tract infection
         subjects affected / exposed
    7 / 103 (6.80%)
    9 / 99 (9.09%)
    3 / 87 (3.45%)
    4 / 88 (4.55%)
         occurrences all number
    13
    18
    3
    5
    Conjunctivitis
         subjects affected / exposed
    8 / 103 (7.77%)
    8 / 99 (8.08%)
    2 / 87 (2.30%)
    3 / 88 (3.41%)
         occurrences all number
    25
    19
    3
    5
    Rhinitis
         subjects affected / exposed
    6 / 103 (5.83%)
    8 / 99 (8.08%)
    3 / 87 (3.45%)
    1 / 88 (1.14%)
         occurrences all number
    12
    13
    4
    1
    Cystitis
         subjects affected / exposed
    7 / 103 (6.80%)
    5 / 99 (5.05%)
    1 / 87 (1.15%)
    1 / 88 (1.14%)
         occurrences all number
    10
    8
    1
    1
    Nasopharyngitis
         subjects affected / exposed
    6 / 103 (5.83%)
    5 / 99 (5.05%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences all number
    6
    5
    1
    0
    Lung infection
         subjects affected / exposed
    1 / 103 (0.97%)
    0 / 99 (0.00%)
    5 / 87 (5.75%)
    4 / 88 (4.55%)
         occurrences all number
    1
    0
    6
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    20 / 103 (19.42%)
    26 / 99 (26.26%)
    34 / 87 (39.08%)
    22 / 88 (25.00%)
         occurrences all number
    38
    52
    54
    30
    Hypoalbuminaemia
         subjects affected / exposed
    5 / 103 (4.85%)
    5 / 99 (5.05%)
    6 / 87 (6.90%)
    4 / 88 (4.55%)
         occurrences all number
    10
    12
    10
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 May 2012
    This amendment concerns the addition of 10% additional patients in order to take into account patients who will not be evaluable, the clarification of the inclusion criteria, the addition of the actions to be taken according to the toxicities of gefitinib, the addition of side effects of fulvestrant and various corrections in particular in the statistical part.
    10 Dec 2012
    This amendment concerns: - the addition of new investigation centers - the removal of three centres: Lille Oscar Lambret, Maubeuge polyclinic and Saint-Omer - the change of address of one center (Toulon CHI) - the elimination of the realization of the partial pressure of oxygen at inclusion - the removal of the QLQ-C30 questionnaire - minor protocol fixes.
    07 May 2015
    This amendment concerns: - extension of the study - the change of investigator for five centres: Le Mans CHG, Dax, Reims CHU, Clamart, Bobigny - the addition in the protocol of a maximum delay in the start of treatment - clarification of the non-inclusion criterion for patients who have already received an experimental drug. - modification of the non-inclusion criterion on anticoagulants - the addition of an additional ancillary study

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32144133
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Sun May 05 16:54:43 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA