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Clinical Trial Results:
A phase II study of the anti-PDL1 antibody atezolizumab, bevacizumab and acetylsalicylic acid to investigate safety and efficacy of this combination in recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal adenocarcinoma

Summary
EudraCT number	2015-004601-17
Trial protocol	ES FR NL GB
Global end of trial date	16 Feb 2022

Results information
Results version number	v1(current)
This version publication date	03 Feb 2023
First version publication date	03 Feb 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

1508-GCG

ISRCTN number

US NCT number

NCT02659384

WHO universal trial number (UTN)

Sponsor organisation name

EORTC

Sponsor organisation address

Avenue E. Mounier 83, Brussels, Belgium, 1200

Public contact

Clinical Operations Unit, European Organisation For Research and Treatment of Cancer (EORTC), 32 2774 10 15, regulatory@eortc.be

Scientific contact

Clinical Operations Unit, European Organisation For Research and Treatment of Cancer (EORTC), 32 2774 10 15, regulatory@eortc.be

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

22 Apr 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

16 Feb 2022

Global end of trial reached?

Yes

Global end of trial date

16 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study is to evaluate the efficacy and safety of 5 different treatments involving atezolizumab, bevacizumab and/or acetylsalicylic acid in advanced recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer patients in order to select the optimal treatments for further development in phase III.

Protection of trial subjects

The study is conducted in agreement with the Declaration of Helsinki (available on the World Medical Association web site (http://www.wma.net)) and/or the laws and regulations of the participating countries, whichever provides the greatest protection of the patient. The protocol has been written, and the study conducted according to the ICH Harmonized Tripartite Guideline on Good Clinical Practice. The protocol was approved by the competent ethics committee(s) as required by the applicable national legislation. Safety data were reviewed within the EORTC Headquarters on a regular basis as part of the Medical Review process. Safety information was included in trial status reports which served as a basis of discussion during EORTC Group meetings.

Background therapy

None.

Evidence for comparator

Work from Coukos et al. as well as other groups has provided evidence that ovarian tumors are spontaneously recognized and attacked by the immune system in many patients, and that the presence of tumor-infiltrating lymphocytes (TILs) is associated with improved outcome. This suggests that immune therapy could produce substantial clinical benefits in ovarian cancer, which is supported by pilot clinical data. It has been demonstrated that increased levels of intratumoral VEGF are associated with absence of TILs in human ovarian cancer. Tumor endothelial cells express Fas ligand (FasL), killing activated lymphocytes and in particular effector cells while immune-suppressive regulatory T cells (Tregs) seem to be resistant to FasL induced cell death. In addition, expression of FasL on tumor endothelial cells was induced by prostaglandin E2 (PGE2) produced at high levels by tumor cells expressing COX1. The effect of PGE2 on FasL expression was further amplified by vascular endothelial growth factor A (VEGF-A), also produced by tumor cells. In several mouse tumor models the administration of acetylsalicylic acid (ASA) to irreversibly inhibit the constitutively expressed COX1 as well as the inducible COX2 combined with anti-VEGF antibody resulted in reduced tumor growth, which was associated and mediated by increased T cell infiltration. Thus, blockade of VEGF and PGE2 in ovarian cancer can reverse the endothelial barrier and allow T cell infiltration, which is expected to synergize with T cell activation by PD-L1 blockade. In the EORTC 1508 trial we propose to combine an anti-PDL1 antibody atezolizumab, to relieve suppression of effector T cells, with bevacizumab and the irreversible COX1/2 inhibitor ASA (acetlysalicyclic acid), with the goal to downregulate the expression of FasL on tumor endothelial cells, ablating the barrier that keeps effector lymphocytes out of the tumor.

Actual start date of recruitment

14 Oct 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

United Kingdom: 30

Country: Number of subjects enrolled

France: 20

Country: Number of subjects enrolled

Switzerland: 26

Country: Number of subjects enrolled

Netherlands: 36

Worldwide total number of subjects

122

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Between 22 December 2016 and 27 February 2020, 122 patients were recruited by 12 centers from 5 countries (Netherlands, United Kingdom, Switzerland, France and Spain).

Screening details

Recurrent, histologically proven, platinum-resistant, epithelial ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage. Age ≥18 years. Life expectancy of ≥ 12 weeks. Adequate hematologic and end organ function. Written informed consent must be given according to ICH/GCP, and national/local regulations.

Period 1 title

Overall study period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

The trial design is partially blind. Only the ASA administration is masked from the patient and local staff through placebo use. The clinical trial administrative personnel (not at the local hospital) remains aware of the actual treatment arm allocation. Allocation of bevacizumab and atezolizumab is not blinded. This blinding system was implemented as ASA can be purchased by patients outside of the trial. Therefore blinding of ASA allocation was enforced to avoid self-medication by the patient.

Are arms mutually exclusive

Yes

bevacizumab mono

Arm description

Bevacizumab 15 mg/kg q3w will be administered as bevacizumab monotherapy treatment and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first. Patients will cross-over to the combination of bevacizumab and atezolizumab upon progression as long as they meet cross-over criteria.

Arm type

Active comparator

Investigational medicinal product name

bevacizumab

Investigational medicinal product code

rhuMAb VEGF

Other name

Avastin

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Parenteral use

Dosage and administration details

Bevacizumab 15 mg/kg q3w will be administered as bevacizumab monotherapy treatment and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

atezolizumab + placebo

Arm description

atezolizumab 1200 mg flat dose q3w will be administered together with placebo 320 mg/d as combination treatment and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first. Patients will cross-over to the combination of bevacizumab and atezolizumab upon progression as long as they meet cross-over criteria

Arm type

Active comparator

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

MPDL3280A

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

atezolizumab 1200 mg flat dose q3w will be administered and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

atezolizumab + ASA

Arm description

atezolizumab 1200 mg flat dose q3w will be administered together with ASA 320 mg/d as combination treatment and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first. Patients will cross-over to the combination of bevacizumab and atezolizumab upon progression as long as they meet cross-over criteria

Arm type

Active comparator

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

MPDL3280A

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

atezolizumab 1200 mg flat dose q3w will be administered and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

atezolizumab + bevacizumab + placebo

Arm description

atezolizumab 1200 mg flat dose q3w will be administered together with bevacizumab 15 mg/kg q3w and placebo 320 mg/d as combination treatment and discontinued upon treatment failure or upon treatment withdrawal, whichever occurs first. Patients then go off protocol treatment and further treatment is left to the investigator’s decision.

Arm type

Active comparator

Investigational medicinal product name

bevacizumab

Investigational medicinal product code

rhuMAb VEGF

Other name

Avastin

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Parenteral use

Dosage and administration details

Bevacizumab 15 mg/kg q3w will be administered as bevacizumab monotherapy treatment and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

MPDL3280A

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

atezolizumab 1200 mg flat dose q3w will be administered and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

atezolizumab + bevacizumab + ASA

Arm description

atezolizumab 1200 mg flat dose q3w will be administered together with bevacizumab 15 mg/kg q3w and ASA 320 mg/d as combination treatment and discontinued upon treatment failure or upon treatment withdrawal, whichever occurs first. Patients then go off protocol treatment and further treatment is left to the investigator’s decision.

Arm type

Active comparator

Investigational medicinal product name

bevacizumab

Investigational medicinal product code

rhuMAb VEGF

Other name

Avastin

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Parenteral use

Dosage and administration details

Bevacizumab 15 mg/kg q3w will be administered as bevacizumab monotherapy treatment and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

MPDL3280A

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

atezolizumab 1200 mg flat dose q3w will be administered and discontinued upon RECISTv1.1-documented progression or upon treatment withdrawal, whichever occurs first.

Number of subjects in period 1	bevacizumab mono	atezolizumab + placebo	atezolizumab + ASA	atezolizumab + bevacizumab + placebo	atezolizumab + bevacizumab + ASA
Started	33	11	13	32	33
Completed	33	11	13	32	33

Baseline characteristics

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Reporting group title

bevacizumab mono

Reporting group description

Reporting group title

atezolizumab + placebo

Reporting group description

Reporting group title

atezolizumab + ASA

Reporting group description

Reporting group title

atezolizumab + bevacizumab + placebo

Reporting group description

Reporting group title

atezolizumab + bevacizumab + ASA

Reporting group description

Reporting group values	bevacizumab mono	atezolizumab + placebo	atezolizumab + ASA	atezolizumab + bevacizumab + placebo	atezolizumab + bevacizumab + ASA	Total
Number of subjects	33	11	13	32	33	122
Age categorical
Age categorical
Units: Subjects
Adults (18-64 years)	18	2	8	20	18	66
From 65-84 years	15	9	5	12	15	56
Age continuous
Age continuous
Units: years
median (full range (min-max))	64 (36 to 75)	70 (47 to 80)	60 (43 to 78)	59.5 (40 to 80)	63 (40 to 82)	-
Gender categorical
Gender categorical
Units: Subjects
Female	33	11	13	32	33	122
Male	0	0	0	0	0	0
WHO PS
WHO performance status
Units: Subjects
WHO PS 0	14	5	7	13	23	62
WHO PS 1	19	6	5	19	10	59
WHO PS 2	0	0	1	0	0	1
Primary tumour site
Primary tumour site
Units: Subjects
ovary	25	9	10	30	26	100
fallopian tube	3	1	1	2	4	11
peritoneum	5	1	2	0	2	10
other	0	0	0	0	1	1
FIGO stage
FIGO stage
Units: Subjects
FIGO I	1	1	1	1	0	4
FIGO II	1	0	0	2	1	4
FIGO III	22	6	7	21	19	75
FIGO IV	9	4	5	7	13	38
Unknown	0	0	0	1	0	1
Months since initial diagnosis
Time in months between initial diagnosis of the primary cancer and date of randomization
Units: months
median (full range (min-max))	44.0 (9.5 to 117.8)	52.5 (26.8 to 131.9)	41.9 (27.0 to 74.2)	44.8 (23.9 to 133.7)	39.8 (17.4 to 135.0)	-

Subject analysis set title

ITT set

Subject analysis set type

Intention-to-treat

Subject analysis set description

All randomized patients according to allocated treatment arm

Subject analysis set title

PFS6 analysis set

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

The primary endpoint was the progression free survival rate at 6 months (PFS-6) defined as the number of patients who are alive and without confirmed progression at month 6 + 1 week after randomization divided by the number of patients known to be alive or dead at month 6 + 1 week after randomization per treatment arm. Two randomized patients with incomplete follow-up prior to month 6 are excluded from the PFS-6 endpoint: one patient withdrew consent at the time of randomization and received no protocol treatment. A second patient received an immunosuppressor (tocilizumab) due to toxicity, which is a medication prohibited by the protocol. This patient was lost-to-follow-up shortly thereafter. Patients included in the Atezolizumab+ASA and Atezolizumab+Placebo arms are excluded as these arms were closed prematurely due to inefficiency.

Subject analysis sets values	ITT set	PFS6 analysis set
Number of subjects	122	96
Age categorical
Age categorical
Units: Subjects
Adults (18-64 years)	66
From 65-84 years	56
Age continuous
Age continuous
Units: years
median (full range (min-max))	62.5 (36 to 82)
Gender categorical
Gender categorical
Units: Subjects
Female	122
Male	0
WHO PS
WHO performance status
Units: Subjects
WHO PS 0	62	49
WHO PS 1	59	47
WHO PS 2	1	0
Primary tumour site
Primary tumour site
Units: Subjects
ovary	100	79
fallopian tube	11	9
peritoneum	10	7
other	1	1
FIGO stage
FIGO stage
Units: Subjects
FIGO I	4	2
FIGO II	4	4
FIGO III	75	61
FIGO IV	38	28
Unknown	1	1
Months since initial diagnosis
Time in months between initial diagnosis of the primary cancer and date of randomization
Units: months
median (full range (min-max))	43.3 (9.5 to 135.0)	43.3 (15.6 to 135.0)

End points

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Reporting group title

bevacizumab mono

Reporting group description

Reporting group title

atezolizumab + placebo

Reporting group description

Reporting group title

atezolizumab + ASA

Reporting group description

Reporting group title

atezolizumab + bevacizumab + placebo

Reporting group description

Reporting group title

atezolizumab + bevacizumab + ASA

Reporting group description

Subject analysis set title

ITT set

Subject analysis set type

Intention-to-treat

Subject analysis set description

All randomized patients according to allocated treatment arm

Subject analysis set title

PFS6 analysis set

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Primary: PFS at 6 months

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End point title

PFS at 6 months

End point description

The primary endpoint is PFS at 6 months (PFS-6) as assessed by the local investigator according to RECIST 1.1. This is defined as the number of patients who are alive and without confirmed progression at month 6 + 1 week after randomization divided by the number of patients known to be alive or dead at month 6 + 1 week after randomization per treatment arm. Patients with incomplete follow-up prior to month 6 are not included.

End point type

Primary

End point timeframe

6 months after randomization

End point values	bevacizumab mono	atezolizumab + placebo	atezolizumab + ASA	atezolizumab + bevacizumab + placebo	atezolizumab + bevacizumab + ASA	PFS6 analysis set
Number of subjects analysed	32	11	13	32	32	96
Units: patients
Alive without progression	7	1	3	8	8	23
Dead or progressed	25	10	10	24	24	73

A'hern test for bevacizumab mono

Statistical analysis description

In order to consider a treatment arm successful, an increase from 30% to 50% PFS-6 would need to be observed within that arm. An A’hern design will first be applied within each arm independently which would require at least 12 out of 29 patients alive and progression-free at month 6.

Comparison groups

bevacizumab mono v PFS6 analysis set

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

< 0.15 ^[2]

Method

binary decision rule

Parameter type

proportion

Point estimate

24.1

Confidence interval

level

95%

sides

2-sided

lower limit

10.3

upper limit

43.5

Notes
[1] - In order to consider a treatment arm successful, an increase from 30% to 50% PFS-6 would need to be observed within that arm. An A’hern design will first be applied within each arm independently which would require at least 12 out of 29 patients alive and progression-free at month 6. This decision rule was applied to the first 29 patients in each arm.
[2] - An A’hern design was applied within each arm independently to test the null hypothesis (H0: PFS-6 = 30%) against the alternative (H1: PFS-6 = 50%) at 1-sided 15% significance level and 85% power.

A'hern test for Bevacizumab+Atezolizumab+Placebo

Statistical analysis description

Comparison groups

atezolizumab + bevacizumab + placebo v PFS6 analysis set

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

< 0.15 ^[4]

Method

binary decision rule

Parameter type

proportion

Point estimate

20.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

39.7

Notes
[3] - In order to consider a treatment arm successful, an increase from 30% to 50% PFS-6 would need to be observed within that arm. An A’hern design will first be applied within each arm independently which would require at least 12 out of 29 patients alive and progression-free at month 6. This decision rule was applied to the first 29 patients in each arm.
[4] - An A’hern design was applied within each arm independently to test the null hypothesis (H0: PFS-6 = 30%) against the alternative (H1: PFS-6 = 50%) at 1-sided 15% significance level and 85% power.

A'hern test for Bevacizumab+Atezolizumab+ASA

Statistical analysis description

Comparison groups

atezolizumab + bevacizumab + ASA v PFS6 analysis set

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

< 0.15 ^[6]

Method

binary decision rule

Parameter type

proportion

Point estimate

27.6

Confidence interval

level

95%

sides

2-sided

lower limit

12.7

upper limit

47.2

Notes
[5] - In order to consider a treatment arm successful, an increase from 30% to 50% PFS-6 would need to be observed within that arm. An A’hern design will first be applied within each arm independently which would require at least 12 out of 29 patients alive and progression-free at month 6. This decision rule was applied to the first 29 patients in each arm.
[6] - An A’hern design was applied within each arm independently to test the null hypothesis (H0: PFS-6 = 30%) against the alternative (H1: PFS-6 = 50%) at 1-sided 15% significance level and 85% power.

Secondary: PFS

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End point title

PFS

End point description

Progression-free survival (PFS) is defined as the time between the date of randomization and the date of first documented progression or death (whatever the cause), whichever occurs first. For patients who remain alive and whose disease has not recurred, PFS will be censored on the date of last visit/contact with disease assessments. PFS will be based on the disease assessment or date of death provided by the local investigator.

End point type

Secondary

End point timeframe

From randomization to end of trial completion.

End point values	bevacizumab mono	atezolizumab + placebo	atezolizumab + ASA	atezolizumab + bevacizumab + placebo	atezolizumab + bevacizumab + ASA
Number of subjects analysed	33	11	13	32	33
Units: months
median (confidence interval 95%)	2.3 (2.0 to 4.1)	2.1 (0.9 to 2.5)	2.2 (1.5 to 4.2)	4.1 (2.2 to 5.4)	4.0 (2.3 to 5.7)

PFS: Bev mono vs Bev+Ate+Pbo

Statistical analysis description

Comparison of the progression free survival in the Bevacizumab + Atezolizumab + Placebo arm to the Bevacizumab monotherapy arm.

Comparison groups

bevacizumab mono v atezolizumab + bevacizumab + placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.801 ^[8]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.38

Notes
[7] - Comparison of the progression free survival in the Bevacizumab + Atezolizumab + Placebo arm to the Bevacizumab monotherapy arm.
[8] - Logrank test

PFS: Bev mono vs Bev+Ate+ASA

Statistical analysis description

Comparison of the progression free survival in the Bevacizumab + Atezolizumab + ASA arm to the Bevacizumab monotherapy arm.

Comparison groups

atezolizumab + bevacizumab + ASA v bevacizumab mono

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.561 ^[10]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.34

Notes
[9] - Comparison of the progression free survival in the Bevacizumab + Atezolizumab + ASA arm to the Bevacizumab monotherapy arm.
[10] - Logrank test

Secondary: Overall survival

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End point title

Overall survival

End point description

Overall survival (OS) is defined as the time from the date of randomization to the date of death, whatever the cause. The follow-up of patients still alive will be censored at the moment of last visit/contact.

End point type

Secondary

End point timeframe

From randomization until end of trial completion

End point values	bevacizumab mono	atezolizumab + placebo	atezolizumab + ASA	atezolizumab + bevacizumab + placebo	atezolizumab + bevacizumab + ASA
Number of subjects analysed	33	11	13	32	33
Units: months
median (confidence interval 95%)	10.4 (5.6 to 13.0)	9.6 (2.4 to 21.7)	16.2 (1.8 to 31.1)	12.1 (6.0 to 14.1)	11.6 (8.8 to 24.7)

OS: Bev mono vs Bev+Ate+Pbo

Statistical analysis description

Comparison of the overall survival in the Bevacizumab + Atezolizumab + Placebo to the Bevacizumab monotherapy arm.

Comparison groups

bevacizumab mono v atezolizumab + bevacizumab + placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.752 ^[12]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.6

Notes
[11] - Comparison of the overall survival in the Bevacizumab + Atezolizumab + Placebo to the Bevacizumab monotherapy arm.
[12] - Logrank test

OS: Bev mono vs Bev+Ate+ASA

Statistical analysis description

Comparison of the overall survival in the Bevacizumab + Atezolizumab + ASA to the Bevacizumab monotherapy arm.

Comparison groups

bevacizumab mono v atezolizumab + bevacizumab + ASA

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.2 ^[14]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.32

Notes
[13] - Comparison of the overall survival in the Bevacizumab + Atezolizumab + ASA to the Bevacizumab monotherapy arm.
[14] - Logrank test

Adverse events

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Timeframe for reporting adverse events

Adverse events were recorded as they occur and graded according to the CTCAE version 4.0 from time of first protocol treatment administration until 30 days after last protocol treatment or if deemed related to study participation.

Adverse event reporting additional description

AEs are evaluated using CTCAE v4 grading, SAEs using MedDra. AEs were also derived from laboratory toxicities if grade ≥3 and all laboratory toxicities that triggered a treatment modification, if not reported on an AE form, were added.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Safety population Bev mono arm

Reporting group description

All patients who have started their allocated treatment (at least one dose) in the Bevacizumab monotherapy arm.

Reporting group title

Safety population Bev+Ate+ASA

Reporting group description

All patients who have started their allocated treatment (at least one dose) in the Bevacizumab + Atezolizumab + ASA arm.

Reporting group title

Safety population Bev+Ate+Pbo

Reporting group description

All patients who have started their allocated treatment (at least one dose) in the Bevacizumab + Atezolizumab + Placebo arm.

Serious adverse events	Safety population Bev mono arm	Safety population Bev+Ate+ASA	Safety population Bev+Ate+Pbo
Total subjects affected by serious adverse events
subjects affected / exposed	15 / 31 (48.39%)	14 / 33 (42.42%)	12 / 31 (38.71%)
number of deaths (all causes)	22	22	21
number of deaths resulting from adverse events	2	0	2
Investigations
ALANINE AMINOTRANSFERASE INCREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ASPARTATE AMINOTRANSFERASE INCREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BLOOD BILIRUBIN INCREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PLATELET COUNT DECREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WHITE BLOOD CELL COUNT DECREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
FRACTURE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILATION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CARDIAC ARREST
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
CARDIAC DISORDER, OTHER : CORONARY SPASM
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEART FAILURE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYOCARDITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUNESS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENCEPHALOPATHY
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
ANAEMIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
FATIGUE
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEVER
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FLU LIKE SYMPTOMS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
AUTOIMMUNE DISORDER
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	4 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
AUTOIMMUNE TOXICITY
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHECKPOINT INHIBITOR IMMUNE INDUCED ENCEPHALITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYTOKINE RELEASE SYNDROME
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
ABDOMINAL PAIN
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANAL HAEMORRHAGE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BOWEL OBSTRUCTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLONIC PERFORATION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLONIC ULCER
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CONSTIPATION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIARRHEA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTRIC HEMORRHAGE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
GASTRITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL DISORDER, OTHER: COPROSTASIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL DISORDER, OTHER: SMALL BOWEL PERFORATION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL DISORDER, OTHER: SMALL INTESTINAL OBSTRUCTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL DISORDERS, OTHER : GASTROENTERITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL FISTULA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ILEAL PERFORATION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NAUSEA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RECTAL PAIN
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SMALL INTESTINAL STENOSIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VOMITING
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
DYSPNEA
alternative dictionary used: MedDRA 24
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PLEURITIC PAIN
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY EDEMA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Renal and urinary disorders
ACUTE KIDNEY INJURY
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYDRONEPHROSIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINAY RETENTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
BACK PAIN
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
ABDOMINAL INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19 INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
FLU LIKE SYMPTOMS
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFECTIOUS PNEUMONITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LUNG INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PELVIC INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PERITONEAL INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
SEPSIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	3 / 31 (9.68%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
STOMA SITE INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	4 / 31 (12.90%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VAGINAL INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Safety population Bev mono arm	Safety population Bev+Ate+ASA	Safety population Bev+Ate+Pbo
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 31 (100.00%)	33 / 33 (100.00%)	31 / 31 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASMS BENIGN - OTHER, BILATERAL BREAST NODULES
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
NEOPLASMS BENIGN - OTHER, PITUITARY CYSTIC LESION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
TUMOR PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	0	1	2
TUMOUR PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Vascular disorders
FINGERS PERIPHERAL VASOCONSTRICTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HEMATOMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	0	1	1
HOT FLASHES
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	3 / 31 (9.68%)
occurrences all number	2	0	4
HYPERTENSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	11 / 31 (35.48%)	10 / 33 (30.30%)	9 / 31 (29.03%)
occurrences all number	23	37	23
LYMPHEDEMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
OCCLUSIVE SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
THROMBOEMBOLIC EVENT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
VASCULAR DISORDERS - OTHER, CYANOSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
VASCULAR DISORDERS - OTHER, PROMINENT CHEST VEINS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
General disorders and administration site conditions
ABDOMINAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0
ASTENIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
ASTHENIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	2
EDEMA LIMBS
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	4 / 33 (12.12%)	6 / 31 (19.35%)
occurrences all number	4	4	7
EDEMA RIGHT LOWER LIMB
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
FATIGUE
alternative dictionary used: CTCAE 4
subjects affected / exposed	21 / 31 (67.74%)	16 / 33 (48.48%)	17 / 31 (54.84%)
occurrences all number	33	26	24
FEVER
alternative dictionary used: CTCAE 4
subjects affected / exposed	6 / 31 (19.35%)	12 / 33 (36.36%)	5 / 31 (16.13%)
occurrences all number	10	20	6
FLU LIKE SYMPTOMS
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 31 (16.13%)	7 / 33 (21.21%)	4 / 31 (12.90%)
occurrences all number	6	11	5
GAIT DISTURBANCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
GENERAL DISORDERS - OTHER, ARM DISCOMFORT
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GENERAL DISORDERS - OTHER, NIGHT SWEATS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
INFUSION RELATED REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	2	0	2
INFUSION SITE EXTRAVASATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
INGUINAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
INJECTION SITE REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
LOCALIZED EDEMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
MALAISE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	2	0	1
NIGHT SWEAT
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
NON-CARDIAC CHEST PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	2	0
PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	3	1	2
PERIPHERAL EDEMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
SHIVERING
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
WEIGHT GAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
WEIGT LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
Immune system disorders
ALLERGIC REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	3	1	3
AUTOIMMUNE DISORDER
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	3 / 33 (9.09%)	1 / 31 (3.23%)
occurrences all number	1	6	1
AUTOIMMUNE TOXICITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
CHECKPOINT INHIBITOR IMMUNE INDUCED ENCEPHALITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
CYTOKINE RELEASE SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
Reproductive system and breast disorders
BREAST DISORDERS - OTHER, THICKNESS OF L BREAST
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
BREAST DISORDERS, OTHER - BREAST HARDENING (L)
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
REPRODUCTIVE SYSTEM DISORDERS - OTHER, VULVAR MUCOSITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
UTERINE HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	2	0
VAGINAL DISCHARGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
VAGINAL DRYNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
VAGINAL HEMORRAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
VAGINAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	2	3	0
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	0	1	2
ATELECTASIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
BREATHLESSNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
COUGH
alternative dictionary used: CTCAE 4
subjects affected / exposed	7 / 31 (22.58%)	5 / 33 (15.15%)	4 / 31 (12.90%)
occurrences all number	7	5	6
DYSPNEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	13 / 31 (41.94%)	8 / 33 (24.24%)	8 / 31 (25.81%)
occurrences all number	16	9	8
EPISTAXIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	4	3	2
HICCUPS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
HOARSENESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	8 / 33 (24.24%)	6 / 31 (19.35%)
occurrences all number	3	8	6
INFECTION UPPER RESPIRATORY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
LARYNGEAL INFLAMMATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
NASAL CONGESTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
PLEURAL EFFUSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
PLEURITIC PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	3 / 31 (9.68%)
occurrences all number	0	0	3
PNEUMONITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0
PRODUCTIVE COUGH
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PULMONARY EDEMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
'RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
RHINORRHEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SORE THROAT
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	2	2	0
Psychiatric disorders
ANXIETY
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	3	2	0
CONFUSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	2	0	2
DEPRESSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HALLUCINATIONS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
INSOMNIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	4	0	1
Investigations
ALANINE AMINOTRANSERASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
ALANINE AMINOTRANSFERASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	4 / 33 (12.12%)	3 / 31 (9.68%)
occurrences all number	4	4	4
ALKALINE PHOSPHATASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	4 / 33 (12.12%)	0 / 31 (0.00%)
occurrences all number	9	5	0
ALP INCREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
ALT INCREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
AMYLASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	1
APTT INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
ASPARTATE AMINOTRANSFERASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	4 / 33 (12.12%)	5 / 31 (16.13%)
occurrences all number	3	6	5
AST INCREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
BLOOD BILIRUBIN INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
CARDIAC TROPONIN T INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
CREATININE INCREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	2	0	1
CREATININE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	4	1	1
CRP INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
FOLATE DEFICIT
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GGT INCREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	3
GGT INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	4	3	0
HYPERKALEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
INVESTIGATION OTHER: WHITE BLOOD CELL INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
INVESTIGATIONS - OTHER, PT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
LDH INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
LIPASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	5 / 33 (15.15%)	3 / 31 (9.68%)
occurrences all number	3	6	5
LYMPHOCYTE COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	5 / 33 (15.15%)	1 / 31 (3.23%)
occurrences all number	3	13	2
LYMPHOCYTES COUNT DECREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
LYMPHOPENIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	2
NEUTROPHIL COUNT DECREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
PLATELET COUNT DECREASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	3
NEUTROPHIL COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	3 / 33 (9.09%)	2 / 31 (6.45%)
occurrences all number	1	5	7
PLATELET COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	5 / 33 (15.15%)	6 / 31 (19.35%)
occurrences all number	2	7	9
WEIGH LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
SERUM AMYLASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	5 / 33 (15.15%)	4 / 31 (12.90%)
occurrences all number	3	6	5
WEIGHT GAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	4 / 31 (12.90%)
occurrences all number	1	1	6
WEIGHT LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	12 / 31 (38.71%)	7 / 33 (21.21%)	11 / 31 (35.48%)
occurrences all number	16	16	17
WHITE BLOOD CELL COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
WHITE BLOOD CELLS DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
WHITE BLOOD CELL DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	4 / 33 (12.12%)	3 / 31 (9.68%)
occurrences all number	0	7	5
Injury, poisoning and procedural complications
BRUISING
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	1	2	0
FRACTURE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
Cardiac disorders
ATRIAL FIBRILATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
CARDIAC ARREST
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
CARDIAC DISORDER, OTHER : CORONARY SPASM
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HEART FAILURE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	2
MYOCARDITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PALPITATIONS
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	2	1	2
SINUS TACHYCARDIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	2	1	1
SUPRAVENTRICULAR TACHYCARDIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	4	0
TACHYCARDIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
VENTRICULAR ARRHYTHMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
DIZZINESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	2 / 33 (6.06%)	2 / 31 (6.45%)
occurrences all number	4	2	3
DYSESTHESIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
DYSGEUSIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	2	1	0
DYSGUEUSIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
ENCEPHALOPATHY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HEADACHE
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 31 (16.13%)	4 / 33 (12.12%)	8 / 31 (25.81%)
occurrences all number	9	4	10
HEADACHES
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	2	0
HEADEACHE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
MUSCLE SPASTICITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
NEURALGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	1	0
PARESTHESIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
PERIPHAL SENSORY NEUROPATHY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
PERIPHERAL MOTOR NEUROPATHY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
PERIPHERAL NEUROPATHY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
PERIPHERAL SENSORY NEUROPATHY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	3 / 33 (9.09%)	1 / 31 (3.23%)
occurrences all number	1	3	1
SOMNOLENCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
SPASTICITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SYNCOPE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
THORACIC NEUROGENIC PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
TREMOR
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Blood and lymphatic system disorders
ANAEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	3
ANEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	8 / 31 (25.81%)	7 / 33 (21.21%)	10 / 31 (32.26%)
occurrences all number	17	10	17
HEMOLYTIC UREMIC SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PLATELET COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Ear and labyrinth disorders
EAR PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HEARING IMPAIRED
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HEARING LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
TINNITUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	2	1	1
VERTIGO
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
Eye disorders
BLURRED VISION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	2	0	2
CATARACT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
CONJUNCTIVITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
DRY EYE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	2	0
EYE DISORDERS - OTHER, PUFFY EYES
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
EYE DISORDERS, OTHER: DETERIORATION OF VISUAL ACUITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
WATERING EYES
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ABDOMINAL DISTENSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ABDOMINAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	10 / 31 (32.26%)	7 / 33 (21.21%)	9 / 31 (29.03%)
occurrences all number	23	10	12
ADDOMINAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ANAL HAEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ANAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	1	0
ASCITES
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	2	2	0
BLOATING
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	1	1	1
BOWEL OBSTRUCTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
COLITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	3	0	1
COLONIC PERFORATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
COLONIC ULCER
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0
CONSTIPATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	9 / 31 (29.03%)	16 / 33 (48.48%)	8 / 31 (25.81%)
occurrences all number	12	18	9
DIARRHEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	12 / 31 (38.71%)	7 / 33 (21.21%)	8 / 31 (25.81%)
occurrences all number	23	10	11
DIARRHEOA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
DRY MOUTH
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	4 / 33 (12.12%)	1 / 31 (3.23%)
occurrences all number	2	10	1
DYSPEPSIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	0	1	3
DYSPHAGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	2	3	0
ESOPHAGEAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ESOPHAGITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
FLATULENCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	2
GASTRIC HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GASTRITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GASTROESOPHAGEAL REFLUX DISEASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	2 / 33 (6.06%)	1 / 31 (3.23%)
occurrences all number	3	4	1
GASTROINTESTINAL - OTHER: SMALL INTESTINAL OBSTRUCTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GASTROINTESTINAL DISORDER, OTHER: COPROSTASIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
GASTROINTESTINAL DISORDER, OTHER: COPROSTATIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
GASTROINTESTINAL DISORDER, OTHER: SMALL BOWEL PERFORATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
GASTROINTESTINAL DISORDERS - OTHER, AEROPHAGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
GASTROINTESTINAL DISORDERS - OTHER, GUM BLEEDING
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
GASTROINTESTINAL DISORDERS - OTHER, PYROSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
GASTROINTESTINAL DISORDERS - OTHER: GASTROENTERITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GASTROINTESTINAL DISORDERS, OTHER : GASTROENTERITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
GASTROINTESTINAL FISTULA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
GASTROINTESTINAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	2	1	0
GASTROPARESIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HAEMARRHOIDS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HEMORRHOIDS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ILEAL PERFORATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	2	0
ILEUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	2	0	1
INTESTINAL OCCLUSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
LIP PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
LOWER GASTROINTESTINAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
MELENA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
MUCOSITIS ORAL
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 31 (16.13%)	4 / 33 (12.12%)	2 / 31 (6.45%)
occurrences all number	5	5	2
MUCOSITIS ORAL (EVENTHOUGH NOT AS ACCURATE AS TONSILOLITH)
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
NAUSEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	10 / 31 (32.26%)	6 / 33 (18.18%)	9 / 31 (29.03%)
occurrences all number	19	9	12
ORAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	0	2	1
ORAL MUSCOSITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
ORAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	1	0
OTHER - EPIGASTRIC PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PANCREATITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
RECTAL FISTULA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
RECTAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	3	0
RECTAL MUCOSITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
RECTAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	8	0	0
SMALL INTESTINAL STENOSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
STOMACH PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	2	3	0
TOOTHACHE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
UPPER GASTROINTESTINAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
VOMINTING
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
VOMITING
alternative dictionary used: CTCAE 4
subjects affected / exposed	12 / 31 (38.71%)	8 / 33 (24.24%)	5 / 31 (16.13%)
occurrences all number	27	14	6
Hepatobiliary disorders
HEPATIC INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HEPATITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HEPATITIS VIRAL
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
HEPATOBILIARY DISORDERS - OTHER, HEPATITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
Skin and subcutaneous tissue disorders
ALLERGIC RASH CUTANEOUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
ALOPECIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	2	0
DRY SKIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 31 (16.13%)	4 / 33 (12.12%)	3 / 31 (9.68%)
occurrences all number	5	4	3
ERYTHEMA MULTIFORME
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	1
NAIL DISCOLORATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
NAIL LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PAIN OF SKIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	2	0
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PALMAR-PLANTAR ERYTHRODYSETHESIA SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PLAMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
PRURITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
PRURITUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	3 / 33 (9.09%)	1 / 31 (3.23%)
occurrences all number	5	3	1
RASH
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
RASH ACNEIFORM
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	2 / 31 (6.45%)
occurrences all number	0	2	2
RASH MACULAR
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
RASH MACULO PAPULAR
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
RASH MACULO-PAPULAR
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0
SCALP PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SKIN AND SUBCUT. TISSUE DISORDERS - OTHER, REDNESS LEFT FOOT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
SKIN AND SUBCUTANEOUS DISORDERS, OTHER : ZONA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, RASH
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, XEROSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SKIN AND SUBCUTANEOUS TISSUE DISORDERS: OTHER, RASH
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SKIN OTHER: SKIN ABRASION LEFT FOREARM
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
SKIN ULCERATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	3	0
URTICARIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Renal and urinary disorders
ACUTE KIDNEY INJURY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
BLADDER SPASM
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
CHRONIC KIDNEY DISEASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	2	0
CYSTITIS NONINFECTIVE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	0	1	2
HEMATURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	5
HYDRONEPHROSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
PROTEINURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	6 / 31 (19.35%)	4 / 33 (12.12%)	1 / 31 (3.23%)
occurrences all number	10	17	2
RENAL AND URINARY DISORDERS - OTHER, DYSURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
RENAL AND URINARY DISORDERS - OTHER, HYDRONEPHROSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
RENAL AND URINARY DISORDERS - OTHER, NOCTURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
RENAL AND URINARY DISORDERS - OTHER, RENAL IMPAIRMENT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
RENAL AND URINARY DISORDERS, OTHER, LEUKOCYTURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
RENAL AND URINARY DISORDERS: LEUKOCYTURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
URINARY FREQUENCY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
URINARY INCONTINENCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
URINAY RETENTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Endocrine disorders
ENDOCRINE DISORDER; OTHER: TSH INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
ENDOCRINE DISORDERS - OTHER, INCREASED TSH
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
HIPOTHYROIDISM
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HYPERTHYROIDISM
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	4 / 33 (12.12%)	0 / 31 (0.00%)
occurrences all number	0	5	0
HYPOTHYROIDISM
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	3 / 33 (9.09%)	3 / 31 (9.68%)
occurrences all number	1	3	4
Musculoskeletal and connective tissue disorders
ARTHRALGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	4 / 33 (12.12%)	4 / 31 (12.90%)
occurrences all number	3	5	4
ARTHRITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	5	0
BACK PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	5 / 33 (15.15%)	2 / 31 (6.45%)
occurrences all number	6	6	2
CHEST WALL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	1	1	3
FLANK PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	4	0	1
GENERALIZED MUSCLE WEAKNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
JOINT RANGE OF MOTION DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
LEG CRAMPS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
MUSCLE SPASM
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MUSCLE WEAKNESS LOWER LIMB
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	3
MUSCLE WEAKNESS LOWER LIMBS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MUSCLE WEAKNESS UPPER LIMB
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
MUSCLE WEAKNESS UPPER LIMBS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MUSCULAR OTHER, LEGS CRAMPS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MUSCULOSKELETAL - OTHER, TORSION RIGHT TOE WITH PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
MUSCULOSKELETAL AND CONNECTIVE TISS. DIS.- OTHER, BODY ACHES
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MUSCULOSKELETAL DEFORMITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MUSCULOSKELETAL DISORDER - OTHER: CRAMP INFERIOR LIMB
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
MUSCULOSKELETAL DISORDERS - OTHER, MYOCLONUS SUPERIOR LIMBS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
MYALGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 31 (16.13%)	7 / 33 (21.21%)	1 / 31 (3.23%)
occurrences all number	5	10	1
MYOSITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	1	1	1
NECK PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	4	1	3
OSTEOPOROSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	0	2	1
PAIN EXTREMITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
PAIN IN EXTREMITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 31 (12.90%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	4	1	1
Infections and infestations
ABDOMINAL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	5	0
CATHETER RELATED INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	1
COVID-19 INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	4	0	0
FLU LIKE SYMPTOMS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	1	1	0
GUM INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	2
INFECTION - OTHER: STAPHILOCOCCUS EPIDERMIDIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
INFECTIONS AND INFESTATIONS - OTHER, SHINGLES
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
INFECTIONS AND INFESTATIONS- OTHER: ORAL THRUSH
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
INFECTIONS AND INFESTATIONS, OTHER : VARICELLA ZOSTER
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
INFECTIOUS PNEUMONITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
LIP INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
LUNG INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
MUCOSAL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	4	0
PELVIC INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
PERITONEAL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0
RHINITIS INFECTIVE
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	3	1	1
RHINITUS INFECTIVE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
SEPSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	3	0	0
SKIN INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	2 / 33 (6.06%)	0 / 31 (0.00%)
occurrences all number	0	2	0
STOMA SITE INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	2	0	0
TOOTH INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
UPPER RESPIRATORY INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	4 / 33 (12.12%)	1 / 31 (3.23%)
occurrences all number	3	4	1
URINARY TRACT INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	8 / 31 (25.81%)	5 / 33 (15.15%)	6 / 31 (19.35%)
occurrences all number	9	9	11
URINARY TRACT INFECTION/KLEBSIELLA PNEUMONIAE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
VAGINAL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
VULVAL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
WOUND INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
ANOREXIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	12 / 31 (38.71%)	10 / 33 (30.30%)	7 / 31 (22.58%)
occurrences all number	16	10	13
DEHYDRATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	0	1	1
HYPERCALCEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	5	0	0
HYPERGLYCAEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HYPERGYLCEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HYPERGLYCEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	2 / 31 (6.45%)
occurrences all number	0	0	3
HYPERKALEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HYPOALBUMINEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	2	2	2
HYPERPHOSPHATEMIA INTERMITTENT
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HYPOKALAEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
HYPOCALCEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	1	0	1
HYPOKALEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	3 / 31 (9.68%)
occurrences all number	2	0	3
HYPOMAGNESAEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	1 / 31 (3.23%)
occurrences all number	0	2	2
HYPOMAGNESEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 31 (6.45%)	3 / 33 (9.09%)	3 / 31 (9.68%)
occurrences all number	4	15	3
HYPOMAGNESMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	1 / 33 (3.03%)	0 / 31 (0.00%)
occurrences all number	0	1	0
HYPONATREMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 31 (9.68%)	1 / 33 (3.03%)	2 / 31 (6.45%)
occurrences all number	3	1	3
HYPOPHOSPHATEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	2 / 33 (6.06%)	1 / 31 (3.23%)
occurrences all number	1	2	3
METABOLISM AND NUTRITION DISORDERS: HYPOPREALBUMINEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
NUTRITION DISORDERS - OTHER, EARLY SATIETY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 31 (0.00%)	0 / 33 (0.00%)	1 / 31 (3.23%)
occurrences all number	0	0	1
REDUCED APETITE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 31 (3.23%)	0 / 33 (0.00%)	0 / 31 (0.00%)
occurrences all number	1	0	0

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Were there any global substantial amendments to the protocol? Yes

18 Feb 2019

This amendment resulted in a major impact on the study design. The original study design was composed of 5 arms. Following amendment 7 (protocol version 5.0), the 2 Atezolizumab monotherapy arms (+ ASA/placebo) were closed. The amendment was motivated by the results of the Javelin 200 trial casting doubts on the efficacy of the Atelizumab + ASA/Placebo arms (arms 2 and 3). The results from this phase III study showed that the efficacy of this PD-L1 inhibitor alone in resistant/refractory ovarian cancer failed to achieve the required efficacy criteria for both primary endpoints (OS & PFS). Keeping the Atezolizumab + ASA/Placebo arms open to recruitment, given the Javelin results, would be unethical to the patients as it would put them at risk of being exposed to potentially ineffective yet toxic therapy. At the time of this amendment (18/02/2019), 57 patients had been randomized in the 5 arms, of which 24 in the now defunct arms. The objectives, statistical methodology and sample size for the three remaining arms did not change requiring 32 patients in each of arms 1, 4 and 5. In addition to the closure of the 2 Atezolizumab monotherapy arms, amendment 7 also formalized the change in study coordinator whereby the original study coordinator, Anita Wolfer (Centre Hospitalier Universitaire Vaudois – Lausanne, Switzerland) was replaced by the current study coordinator Susana Banerjee (The Royal Marsden NHS Foundation Trust, London).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Two of the 5 initial treatment arms were discontinued during the course of the study. See amendment section for more details.

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A phase II study of the anti-PDL1 antibody atezolizumab, bevacizumab and acetylsalicylic acid to investigate safety and efficacy of this combination in recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal adenocarcinoma

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Clinical Trial Results: A phase II study of the anti-PDL1 antibody atezolizumab, bevacizumab and acetylsalicylic acid to investigate safety and efficacy of this combination in recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal adenocarcinoma

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Trial information

Subject disposition

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Baseline characteristics

Baseline characteristics

End points

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Primary: PFS at 6 months

Primary: PFS at 6 months

Secondary: PFS

Secondary: PFS

Secondary: Overall survival

Secondary: Overall survival

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A phase II study of the anti-PDL1 antibody atezolizumab, bevacizumab and acetylsalicylic acid to investigate safety and efficacy of this combination in recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal adenocarcinoma