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Clinical Trial Results:
A prospective, open, randomized, phase-II study of a therapeutic cancer vaccine (L-BLP25, Stimuvax®) in the pre-operative treatment of women with primary breast cancer

Summary
EudraCT number	2011-004822-85
Trial protocol	AT
Global end of trial date	10 Apr 2015

Results information
Results version number	v1(current)
This version publication date	14 Aug 2021
First version publication date	14 Aug 2021
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

ABCSG-34

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Other trial identifiers

Merck Code: EMR63325-603

Sponsor organisation name

ABCSG (Austrian Breast & Colorectal Cancer Study Group)

Sponsor organisation address

Nußdorfer Platz 8/12, Vienna, Austria, 1190

Public contact

Hannes Fohler (Trial Office Director), ABCSG (Austrian Breast & Colorectal Cancer Study Group), +43 14089230, info@abcsg.at

Scientific contact

Michael Gnant (ABCSG President and Trial Chair), ABCSG (Austrian Breast & Colorectal Cancer Study Group), +43 14089230, info@abcsg.at

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

10 Apr 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Apr 2015

Global end of trial reached?

Yes

Global end of trial date

10 Apr 2015

Was the trial ended prematurely?

Main objective of the trial

To compare efficacy of pre-operative standard of care treatment with or without a therapeutic cancer vaccine (L-BLP25), measured by Residual Cancer Burden (RCB) at the time of surgery

Protection of trial subjects

The study specific patient information and informed consent form included language to encourage study participants to reach out to the Study Doctor / Study Team in case they have any questions, concerns or doubts. Section 15 specifically referenced a 24/7 contact person to reach out to, the ICF furthermore contained a reference to the local ombudsman / patient advocacy and a study specific patient card was implemented and distributed, containing important information and contact details. A dedicated IDMC was established to ensure patient safety throughout the trial.

Background therapy

Standard of care chemotherapy (Epirubicin, cyclophosphamide, docetaxel) irrespective of sequence.

Evidence for comparator

Actual start date of recruitment

08 May 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 400

Worldwide total number of subjects

400

EEA total number of subjects

400

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)

312

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A careful check of inclusion and exclusion criteria had to be performed by the Investigators / Site Teams and a web based randomization system was subsequently used which assigned treatment arms electronically, i.e. randomized the participants into the previously described treatment arms.

Number of subjects started

400

Number of subjects completed

400

Period 1 title

overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Chemo conv with L-BLP25

Arm description

Patients received SoC and tecemotide (L-BLP25). Neo-adjuvant chemotherapy conventional sequence (Chemo conv) was considered SoC.

Arm type

Experimental

Investigational medicinal product name

L-BLP25 (Stimuvax)

Investigational medicinal product code

EMD531444

Other name

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

4 x 0.5 ml reconstituted L-BLP25 (containing 918 mcg (total of 4 vials) of BLP25 lipopeptide) mg/l milligram(s)/litre

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Endoxana Injection 1g

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

300 mg/m2

Chemo rev with L-BLP25

Arm description

Patients received SoC and tecemotide (L-BLP25). Neo-adjuvant chemotherapy reverse sequence (Chemo rev) was considered SoC.

Arm type

Experimental

Investigational medicinal product name

L-BLP25 (Stimuvax)

Investigational medicinal product code

EMD531444

Other name

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

4 x 0.5 ml reconstituted L-BLP25 (containing 918 mcg (total of 4 vials) of BLP25 lipopeptide) mg/l milligram(s)/litre

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Endoxana Injection 1g

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

300 mg/m2

AI with L-BLP25

Arm description

Patients received SoC and tecemotide (L-BLP25). Preoperative endocrine therapy (AI) was considered SoC.

Arm type

Experimental

Investigational medicinal product name

L-BLP25 (Stimuvax)

Investigational medicinal product code

EMD531444

Other name

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

4 x 0.5 ml reconstituted L-BLP25 (containing 918 mcg (total of 4 vials) of BLP25 lipopeptide) mg/l milligram(s)/litre

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Endoxana Injection 1g

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

300 mg/m2

Investigational medicinal product name

Letrozol

Investigational medicinal product code

Other name

Letrozol Sandoz

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2.5 mg milligram(s)

Chemo conv without L-BLP25

Arm description

Patients received SoC only and no tecemotide (L-BLP25). Neo-adjuvant chemotherapy conventional sequence (Chemo conv) was considered SoC.

Arm type

SOC

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Chemo rev without L-BLP25

Arm description

Patients received SoC only and no tecemotide (L-BLP25). Neo-adjuvant chemotherapy reverse sequence (Chemo rev) was considered SoC.

Arm type

SOC

Investigational medicinal product name

No investigational medicinal product assigned in this arm

AI without L-BLP25

Arm description

Patients received SoC only and no tecemotide (L-BLP25). Preoperative endocrine therapy (AI) was considered SoC.

Arm type

Active comparator

Investigational medicinal product name

Letrozol

Investigational medicinal product code

Other name

Letrozol Sandoz

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2.5 mg milligram(s)

Number of subjects in period 1	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Started	78	79	43	76	78	46
Completed	73	73	41	74	76	44
Not completed	5	6	2	2	2	2
Adverse event, serious fatal	-	1	-	-	1	-
Consent withdrawn by subject	5	5	2	-	-	1
Other	-	-	-	2	-	1
Lost to follow-up	-	-	-	-	1	-

Baseline characteristics

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Reporting group title

Chemo conv with L-BLP25

Reporting group description

Patients received SoC and tecemotide (L-BLP25). Neo-adjuvant chemotherapy conventional sequence (Chemo conv) was considered SoC.

Reporting group title

Chemo rev with L-BLP25

Reporting group description

Patients received SoC and tecemotide (L-BLP25). Neo-adjuvant chemotherapy reverse sequence (Chemo rev) was considered SoC.

Reporting group title

AI with L-BLP25

Reporting group description

Patients received SoC and tecemotide (L-BLP25). Preoperative endocrine therapy (AI) was considered SoC.

Reporting group title

Chemo conv without L-BLP25

Reporting group description

Patients received SoC only and no tecemotide (L-BLP25). Neo-adjuvant chemotherapy conventional sequence (Chemo conv) was considered SoC.

Reporting group title

Chemo rev without L-BLP25

Reporting group description

Patients received SoC only and no tecemotide (L-BLP25). Neo-adjuvant chemotherapy reverse sequence (Chemo rev) was considered SoC.

Reporting group title

AI without L-BLP25

Reporting group description

Patients received SoC only and no tecemotide (L-BLP25). Preoperative endocrine therapy (AI) was considered SoC.

Reporting group values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25	Total
Number of subjects	78	79	43	76	78	46	400
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	73	73	19	69	64	14	312
From 65-84 years	5	6	24	7	14	32	88
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: years
median (full range (min-max))	50 (28 to 73)	49 (25 to 72)	65 (52 to 83)	48 (26 to 78)	47 (26 to 75)	68.5 (52 to 81)	-
Gender categorical
Units: Subjects
Female	78	79	43	76	78	46	400
Male	0	0	0	0	0	0	0
Menopausal Status
Units: Subjects
perimenopausal	27	28	43	29	28	45	200
postmenopausal	5	0	0	3	3	0	11
premenopausal	45	48	0	44	47	1	185
missing	1	3	0	0	0	0	4
Tumor Size
T-stage
Units: Subjects
T1	21	23	19	18	24	20	125
T2/Z3/T4	57	56	23	58	54	26	274
missing	0	0	1	0	0	0	1
Nodal Stage
N-stage
Units: Subjects
negative	53	45	32	41	39	38	248
positive	24	30	11	33	39	8	145
missing	1	4	0	2	0	0	7
Estrogen Receptor
ER
Units: Subjects
negative	31	41	0	37	35	0	144
positive	47	36	43	36	42	46	250
missing	0	2	0	3	1	0	6
Progesterone Receptor
PR
Units: Subjects
negative	40	46	4	36	35	3	164
positive	38	32	39	37	42	42	230
missing	0	1	0	3	1	1	6
BMI
Body Mass Index
Units: score
median (full range (min-max))	24.5 (16.5 to 42.8)	24.3 (15.0 to 39.0)	27.1 (19.1 to 36.3)	24.6 (18.1 to 35.2)	24.5 (18.8 to 40.5)	28.3 (19.9 to 47.6)	-
Ki67
Units: score
median (full range (min-max))	50 (2 to 90)	50 (5 to 95)	10 (3 to 80)	50 (3 to 90)	50 (3 to 90)	10 (1 to 50)	-

End points

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Reporting group title

Chemo conv with L-BLP25

Reporting group description

Patients received SoC and tecemotide (L-BLP25). Neo-adjuvant chemotherapy conventional sequence (Chemo conv) was considered SoC.

Reporting group title

Chemo rev with L-BLP25

Reporting group description

Patients received SoC and tecemotide (L-BLP25). Neo-adjuvant chemotherapy reverse sequence (Chemo rev) was considered SoC.

Reporting group title

AI with L-BLP25

Reporting group description

Patients received SoC and tecemotide (L-BLP25). Preoperative endocrine therapy (AI) was considered SoC.

Reporting group title

Chemo conv without L-BLP25

Reporting group description

Patients received SoC only and no tecemotide (L-BLP25). Neo-adjuvant chemotherapy conventional sequence (Chemo conv) was considered SoC.

Reporting group title

Chemo rev without L-BLP25

Reporting group description

Patients received SoC only and no tecemotide (L-BLP25). Neo-adjuvant chemotherapy reverse sequence (Chemo rev) was considered SoC.

Reporting group title

AI without L-BLP25

Reporting group description

Patients received SoC only and no tecemotide (L-BLP25). Preoperative endocrine therapy (AI) was considered SoC.

Subject analysis set title

ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Since the aim of this phase II study is to detect any effect of tecemotide, a pure intention-to-treat (ITT) analysis based on a conservative worst-case approach may underestimate the effect. Therefore the ITT analysis population includes all randomized patients who are evaluable at the time of final surgery. Patients are analysed according to the treatment to which they have been randomized.

Subject analysis set title

Safety

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population includes all randomized patients with at least one administration of study treatment (investigational and/or non-investigational medical product – IMP and/or NIMP). Patients are analysed according to the treatment they have actually received.

Primary: Residual Cancer Burden (RCB)

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End point title

Residual Cancer Burden (RCB)

End point description

The primary endpoint is histopathological response to pre-operative standard of care (SoC) treatment with or without L-BLP25 therapy when measured by Residual Cancer Burden (RCB) at the time of surgery and is defined by reaching RCB-0 or RCB-I (=RCB index ≤1.36) vs RCB-II or RCB-III (=RCB index >1.36).

End point type

Primary

End point timeframe

at surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	72	72	40	70	73	45
Units: Subjects
RCB 0/I	31	26	10	26	28	6
RCB II/III	41	46	30	44	45	39

Primary endpoint analysis

Statistical analysis description

The proportions of patients exhibiting RCB-0/I are compared between the experimental group (with L-BLP25) and the control group (without L-BLP25) using the Cochran-Mantel-Haenszel test to take into account different prognoses for endocrine therapy (AI) and chemotherapy (chemo). Hence, conventional and reverse chemotherapy patients are considered within one group/arm for this analysis.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

372

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.4024

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[1] - H0: proportion of patients with RCB-0 or RCB-I in the experimental group is equal to that in the control group H1: proportion of patients with RCB-0 or RCB-I in the experimental group differs from that in the control group

Secondary: Pathological Complete Response (pCR)

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End point title

Pathological Complete Response (pCR)

End point description

This secondary endpoint describes the absence of invasive cancer cells in surgical specimen as pathological complete response (pCR) and is defined by pCR yes vs pCR no.

End point type

Secondary

End point timeframe

at surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	73	73	41	75	75	45
Units: Subjects
pCR yes	19	21	2	17	16	1
pCR no	54	52	39	58	59	44

Secondary endpoint analysis - pCR

Statistical analysis description

The proportions of patients exhibiting pCR (=absence of invasive cancer cells in surgical specimen) are compared between the experimental (with L-BLP25) and the control (without L-BLP25) arm using the Cochran-Mantel-Haenszel test to take into account different prognoses for endocrine therapy (AI) and chemotherapy (chemo). Hence, conventional and reverse chemotherapy patients are considered within one group/arm for this analysis.

Comparison groups

Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

382

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2312

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Residual Cancer Burden (RCB) - conv vs rev

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End point title

Residual Cancer Burden (RCB) - conv vs rev ^[2]

End point description

This secondary endpoint describes the efficacy of reverse versus conventional sequence chemotherapy as measured by Residual Cancer Burden (RCB) at the time of surgery and is defined by reaching RCB-0 or RCB-I (=RCB index ≤1.36) vs RCB-II or RCB-III (=RCB index >1.36).

End point type

Secondary

End point timeframe

at surgery

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This analysis was planned to not include all the arms - only chemotherapy arms are compared.

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25
Number of subjects analysed	72	72	70	73
Units: Subjects
RCB 0/I	31	26	26	28
RCB II/III	41	46	44	45

Secondary endpoint analysis - RCB conv vs rev

Statistical analysis description

Proportions of RCB (RCB-0/I versus RCB-II/III) are compared between chemotherapy conventional sequence and chemotherapy reverse sequence using Chi² test within the subset of patients receiving chemotherapy. Hence, with and without L-BLP25 patients are considered within one group/arm for this analysis.

Comparison groups

Chemo rev with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v Chemo conv with L-BLP25

Number of subjects included in analysis

287

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6141

Method

Chi-squared

Confidence interval

Secondary: Tumor Associated Lymphocytes (TAL) - stromal BL

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End point title

Tumor Associated Lymphocytes (TAL) - stromal BL

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by stromal tumor associated lymphocytes (TAL).

End point type

Secondary

End point timeframe

at baseline

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	74	69	40	69	71	44
Units: Percentages
median (full range (min-max))	5 (0 to 80)	5 (0 to 70)	0 (0 to 20)	5 (0 to 70)	5 (0 to 60)	0 (0 to 30)

Secondary endpoint analysis - TAL stromal BL

Statistical analysis description

Proportions of stromal TALs at baseline are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4664

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Tumor Associated Lymphocytes (TAL) - stromal MT

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End point title

Tumor Associated Lymphocytes (TAL) - stromal MT

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by stromal tumor associated lymphocytes (TAL).

End point type

Secondary

End point timeframe

at mid-therapy

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	44	36	37	43	41	38
Units: Percentages
median (full range (min-max))	1 (0 to 40)	5 (0 to 80)	0 (0 to 30)	5 (0 to 60)	1 (0 to 50)	0 (0 to 10)

Secondary endpoint analysis - TAL stromal MT

Statistical analysis description

Proportions of stromal TALs at mid-therapy are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

239

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5276

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Tumor Associated Lymphocytes (TAL) - stromal SU

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End point title

Tumor Associated Lymphocytes (TAL) - stromal SU

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by stromal tumor associated lymphocytes (TAL).

End point type

Secondary

End point timeframe

at surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	41	39	38	49	48	42
Units: Percentages
median (full range (min-max))	1 (0 to 40)	1 (0 to 40)	1 (0 to 40)	1 (0 to 70)	1 (0 to 50)	1 (0 to 30)

Secondary endpoint analysis - TAL stromal SU

Statistical analysis description

Proportions of stromal TALs at surgery are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

257

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5601

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Tumor Associated Lymphocytes (TAL) - stromal BL to MT

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End point title

Change in Tumor Associated Lymphocytes (TAL) - stromal BL to MT

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by changes in stromal tumor associated lymphocytes (TAL) under tumor therapy.

End point type

Secondary

End point timeframe

baseline to mid-therapy

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	44	31	35	39	39	37
Units: Percentages
median (full range (min-max))	-4 (-60 to 35)	0 (-20 to 49)	0 (-10 to 25)	0 (-35 to 55)	0 (-10 to 35)	0 (-29 to 5)

Secondary endpoint analysis - TAL stromal BL to MT

Statistical analysis description

Changes of stromal TALs under tumor therapy (baseline to mid-therapy) are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4497

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Tumor Associated Lymphocytes (TAL) - stromal BL to SU

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End point title

Change in Tumor Associated Lymphocytes (TAL) - stromal BL to SU

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by changes in stromal tumor associated lymphocytes (TAL) under tumor therapy.

End point type

Secondary

End point timeframe

baseline to surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	41	37	37	46	44	41
Units: Percentages
median (full range (min-max))	-4 (-39 to 35)	0 (-40 to 39)	0 (-20 to 39)	-0.5 (-40 to 39)	-1 (-60 to 40)	0 (-25 to 29)

Secondary endpoint analysis - TAL stromal BL to SU

Statistical analysis description

Changes of stromal TALs under tumor therapy (baseline to surgery) are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5251

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral BL

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End point title

Tumor Associated Lymphocytes (TAL) - intratumoral BL

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by intratumoral tumor associated lymphocytes (TAL).

End point type

Secondary

End point timeframe

at baseline

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	74	68	40	68	70	44
Units: Percentages
median (full range (min-max))	5 (0 to 80)	5 (0 to 70)	0 (0 to 40)	5 (0 to 60)	5 (0 to 70)	0 (0 to 30)

Secondary endpoint analysis - TAL intratumoral BL

Statistical analysis description

Proportions of intratumoral TALs at baseline are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

364

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6096

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral MT

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End point title

Tumor Associated Lymphocytes (TAL) - intratumoral MT

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by intratumoral tumor associated lymphocytes (TAL).

End point type

Secondary

End point timeframe

at mid-therapy

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	44	37	37	43	41	38
Units: Percentages
median (full range (min-max))	0 (0 to 30)	1 (0 to 80)	0 (0 to 30)	1 (0 to 80)	1 (0 to 60)	0 (0 to 10)

Secondary endpoint analysis - TAL intratumoral MT

Statistical analysis description

Proportions of intratumoral TALs at mid-therapy are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

240

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7715

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral SU

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End point title

Tumor Associated Lymphocytes (TAL) - intratumoral SU

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by intratumoral tumor associated lymphocytes (TAL).

End point type

Secondary

End point timeframe

at surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	41	39	38	49	48	42
Units: Percentages
median (full range (min-max))	1 (0 to 80)	1 (0 to 50)	0 (0 to 40)	0 (0 to 70)	0 (0 to 70)	0 (0 to 20)

Secondary endpoint analysis - TAL intratumoral SU

Statistical analysis description

Proportions of intratumoral TALs at surgery are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

257

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5959

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to MT

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End point title

Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to MT

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by changes in intratumoral tumor associated lymphocytes (TAL) under tumor therapy.

End point type

Secondary

End point timeframe

baseline to mid-therapy

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	44	32	35	39	39	37
Units: Percentages
median (full range (min-max))	-4 (-60 to 20)	0 (-30 to 79)	0 (-40 to 25)	-1 (-30 to 60)	0 (-50 to 20)	0 (-25 to 5)

Secondary endpoint analysis - TAL intra BL to MT

Statistical analysis description

Changes of intratumoral TALs under tumor therapy (baseline to mid-therapy) are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7325

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to SU

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End point title

Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to SU

End point description

End point type

Secondary

End point timeframe

baseline to surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	41	37	37	46	44	41
Units: Percentages
median (full range (min-max))	-4 (-50 to 70)	0 (-60 to 35)	0 (-40 to 39)	0 (-55 to 50)	-2.5 (-70 to 60)	0 (-29 to 19)

Secondary endpoint analysis - TAL intra BL to SU

Statistical analysis description

Changes of intratumoral TALs under tumor therapy (baseline to surgery) are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.888

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Ki67 tumor status (MIB1) - BL

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End point title

Ki67 tumor status (MIB1) - BL

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by Ki67 tumor status (MIB1).

End point type

Secondary

End point timeframe

at baseline

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	74	72	42	71	72	44
Units: Percentages
median (full range (min-max))	55 (5 to 90)	55 (10 to 90)	20 (5 to 70)	50 (5 to 90)	50 (1 to 80)	20 (5 to 70)

Secondary endpoint analysis - Ki67 BL

Statistical analysis description

Proportions of Ki67 tumor status (MIB1) at baseline are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo rev with L-BLP25 v Chemo conv with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

375

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.649

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Ki67 tumor status (MIB1) - MT

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End point title

Ki67 tumor status (MIB1) - MT

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by Ki67 tumor status (MIB1).

End point type

Secondary

End point timeframe

at mid-therapy

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	45	34	36	44	42	36
Units: Percentages
median (full range (min-max))	20 (1 to 90)	25 (1 to 90)	3 (1 to 10)	15 (1 to 90)	15 (1 to 90)	1 (1 to 30)

Secondary endpoint analysis - Ki67 MT

Statistical analysis description

Proportions of Ki67 tumor status (MIB1) at mid-therapy are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6418

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Ki67 tumor status (MIB1) - SU

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End point title

Ki67 tumor status (MIB1) - SU

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by Ki67 tumor status (MIB1).

End point type

Secondary

End point timeframe

at surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	44	40	38	48	50	42
Units: Percentages
median (full range (min-max))	10 (1 to 80)	30 (1 to 90)	5 (0 to 40)	7.5 (0 to 90)	10 (0 to 80)	1 (0 to 70)

Secondary endpoint analysis - Ki67 SU

Statistical analysis description

Proportions of Ki67 tumor status (MIB1) at surgery are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

262

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1601

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Ki67 tumor status (MIB1) - BL to MT

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End point title

Change in Ki67 tumor status (MIB1) - BL to MT

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by changes in Ki67 tumor status (MIB1) under tumor therapy.

End point type

Secondary

End point timeframe

baseline to mid-therapy

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	45	31	36	42	40	35
Units: Percentages
median (full range (min-max))	-10 (-75 to 20)	-10 (-60 to 40)	-15 (-50 to -4)	-20 (-75 to 20)	-15 (-69 to 40)	-10 (-69 to 0)

Secondary endpoint analysis - Ki67 BL to MT

Statistical analysis description

Changes of Ki67 tumor status (MIB1) under tumor therapy (baseline to mid-therapy) are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5818

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Ki67 tumor status (MIB1) - BL to SU

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End point title

Change in Ki67 tumor status (MIB1) - BL to SU

End point description

This secondary endpoint describes the proportion of patients with “lymphocyte-predominant” breast cancer as measured by changes in Ki67 tumor status (MIB1) under tumor therapy.

End point type

Secondary

End point timeframe

baseline to surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	44	38	38	47	46	41
Units: Percentages
median (full range (min-max))	-19.5 (-79 to 20)	-10 (-70 to 40)	-9 (-50 to 10)	-25 (-79 to 60)	-10 (-70 to 20)	-10 (-65 to 65)

Secondary endpoint analysis - Ki67 BL to SU

Statistical analysis description

Changes of Ki67 tumor status (MIB1) under tumor therapy (baseline to surgery) are described descriptively (median, range) per treatment arm. Due to the skewed distribution of parameters, differences in parameters between treatment arms (with and without L-BLP25) are analysed using Wilcoxon tests. Tests schould not be considered conclusive, but as additional description.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

254

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6003

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Change in Quality of Life (QoL) - BL to SU

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End point title

Change in Quality of Life (QoL) - BL to SU

End point description

This secondary endpoint describes the change in Quality of Life (QoL) from baseline to surgery based on the standardized Quality of Life questionnaires from EORTC, QLQ-C30 (Version 3.0) and QLQ-BR23 (Version 1.0) - example shows the global health score.

End point type

Secondary

End point timeframe

baseline to surgery

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	59	62	31	58	58	32
Units: value
arithmetic mean (standard deviation)	-0.30 ± 1.52	-0.44 ± 1.52	0.15 ± 1.16	-0.41 ± 1.73	-0.59 ± 1.40	0.03 ± 1.55

Secondary endpoint analysis - QoL BL to SU

Statistical analysis description

Changes of quality of life (QoL) under tumor therapy (baseline to surgery) are described descriptively (mean, standrad deviation) per treatment arm - example shows the global health score. A pre-post comparison is done using the Wilcoxon signed-rank test for paired samples.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0001

Method

Wilcoxon signed rank

Confidence interval

Secondary: Change in Quality of Life (QoL) - BL to EOS

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End point title

Change in Quality of Life (QoL) - BL to EOS

End point description

This secondary endpoint describes the change in Quality of Life (QoL) from baseline to end of study (EOS) visit based on the standardized Quality of Life questionnaires from EORTC, QLQ-C30 (Version 3.0) and QLQ-BR23 (Version 1.0) - example shows the global health score.

End point type

Secondary

End point timeframe

baseline to end of study (EOS) visit

End point values	Chemo conv with L-BLP25	Chemo rev with L-BLP25	AI with L-BLP25	Chemo conv without L-BLP25	Chemo rev without L-BLP25	AI without L-BLP25
Number of subjects analysed	52	57	26	53	56	28
Units: value
arithmetic mean (standard deviation)	-0.38 ± 1.83	-0.21 ± 1.47	-0.17 ± 1.33	-0.31 ± 1.53	-0.59 ± 1.63	0.09 ± 1.69

Secondary endpoint analysis - QoL BL to EOS

Statistical analysis description

Changes of quality of life (QoL) under tumor therapy (baseline to end of study (EOS) visit) are described descriptively (mean, standrad deviation) per treatment arm - example shows the global health score. A pre-post comparison is done using the Wilcoxon signed-rank test for paired samples.

Comparison groups

Chemo conv with L-BLP25 v Chemo rev with L-BLP25 v AI with L-BLP25 v Chemo conv without L-BLP25 v Chemo rev without L-BLP25 v AI without L-BLP25

Number of subjects included in analysis

272

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0025

Method

Wilcoxon signed rank

Confidence interval

Adverse events

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Timeframe for reporting adverse events

All SAEs occurring after the patient had signed the Informed Consent until the End of Study Visit must be reported to ABCSG within above mentioned timelines.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

Chemotherapy conventional sequence with L-BLP25

Reporting group description

Reporting group title

Chemotherapy conventional sequence without L-BLP25

Reporting group description

Reporting group title

Chemotherapy reverse sequence with L-BLP25

Reporting group description

Reporting group title

Chemotherapy reverse sequence without L-BLP25

Reporting group description

Reporting group title

Endocrine Aromatase inhibitor therapy with L-BLP25

Reporting group description

Reporting group title

Endocrine Aromatase inhibitor therapy without L-BLP25

Reporting group description

Serious adverse events	Chemotherapy conventional sequence with L-BLP25	Chemotherapy conventional sequence without L-BLP25	Chemotherapy reverse sequence with L-BLP25	Chemotherapy reverse sequence without L-BLP25	Endocrine Aromatase inhibitor therapy with L-BLP25	Endocrine Aromatase inhibitor therapy without L-BLP25
Total subjects affected by serious adverse events
subjects affected / exposed	22 / 77 (28.57%)	19 / 77 (24.68%)	30 / 77 (38.96%)	24 / 78 (30.77%)	5 / 41 (12.20%)	5 / 46 (10.87%)
number of deaths (all causes)	0	0	1	1	0	0
number of deaths resulting from adverse events	0	0	1	1	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
Additional description: Metastases to meninges
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
Additional description: Deep vein thrombosis
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Flushing
Additional description: Flushing
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hot flush
Additional description: Hot flush
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
Additional description: Hypotension
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subclavian vein thrombosis
Additional description: Subclavian vein thrombosis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombophlebitis
Additional description: Thrombophlebitis
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis
Additional description: Thrombosis
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis
Additional description: Venous thrombosis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest discomfort
Additional description: Chest discomfort
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
Additional description: Chest pain
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	1 / 77 (1.30%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Extravasation
Additional description: Extravasation
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
Additional description: Fatigue
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
Additional description: General physical health deterioration
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised oedema
Additional description: Generalised oedema
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Impaired healing
Additional description: Impaired healing
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Implant site extravasation
Additional description: Implant site extravasation
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Medical device complication
Additional description: Medical device complication
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Necrosis
Additional description: Necrosis
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	2 / 77 (2.60%)	2 / 77 (2.60%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Sarcoidosis
Additional description: Sarcoidosis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	1 / 77 (1.30%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngeal oedema
Additional description: Pharyngeal oedema
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
Additional description: Pneumothorax
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
Additional description: Pulmonary embolism
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
Additional description: Alanine aminotransferase increased
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
Additional description: Aspartate aminotransferase increased
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood glucose increased
Additional description: Blood glucose increased
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
C-reactive protein increased
Additional description: C-reactive protein increased
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
Additional description: Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 77 (2.60%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fractured sacrum
Additional description: Fractured sacrum
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint injury
Additional description: Joint injury
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus lesion
Additional description: Meniscus lesion
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pubis fracture
Additional description: Pubis fracture
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seroma
Additional description: Seroma
subjects affected / exposed	0 / 77 (0.00%)	2 / 77 (2.60%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound dehiscence
Additional description: Wound dehiscence
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Epidermolysis
Additional description: Epidermolysis
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 6	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sebaceous naevus
Additional description: Sebaceous naevus
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	1 / 41 (2.44%)	1 / 46 (2.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Balance disorder
Additional description: Balance disorder
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
Additional description: Cerebral infarction
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
Additional description: Headache
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
Additional description: Loss of consciousness
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
Additional description: Sciatica
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Speech disorder
Additional description: Speech disorder
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
Additional description: Febrile neutropenia
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	6 / 77 (7.79%)	6 / 78 (7.69%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 6	0 / 6	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
Additional description: Leukopenia
subjects affected / exposed	3 / 77 (3.90%)	1 / 77 (1.30%)	4 / 77 (5.19%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 5	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenopathy
Additional description: Lymphadenopathy
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	4 / 77 (5.19%)	0 / 77 (0.00%)	3 / 77 (3.90%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 5	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
Additional description: Pancytopenia
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
Additional description: Vertigo
subjects affected / exposed	3 / 77 (3.90%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Conjunctivitis
Additional description: Conjunctivitis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	2 / 77 (2.60%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fissure
Additional description: Anal fissure
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
Additional description: Colitis
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
Additional description: Constipation
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	2 / 77 (2.60%)	3 / 77 (3.90%)	2 / 77 (2.60%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 3	1 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulum intestinal haemorrhagic
Additional description: Diverticulum intestinal haemorrhagic
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
Additional description: Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
Additional description: Dysphagia
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis
Additional description: Enteritis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Faecaloma
Additional description: Faecaloma
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis erosive
Additional description: Gastritis erosive
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glossitis
Additional description: Glossitis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
Additional description: Nausea
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
Additional description: Stomatitis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
Additional description: Vomiting
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 77 (0.00%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Eczema
Additional description: Eczema
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurodermatitis
Additional description: Neurodermatitis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Swelling face
Additional description: Swelling face
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
Additional description: Urticaria
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
Additional description: Renal failure acute
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: Arthralgia
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
Additional description: Bone pain
subjects affected / exposed	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 77 (0.00%)	3 / 78 (3.85%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
Additional description: Osteonecrosis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
Additional description: Abdominal abscess
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute tonsillitis
Additional description: Acute tonsillitis
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
Additional description: Appendicitis
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bartholin's abscess
Additional description: Bartholin's abscess
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
Additional description: Bronchitis
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
Additional description: Bronchopneumonia
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
Additional description: Device related infection
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related sepsis
Additional description: Device related sepsis
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile infection
Additional description: Febrile infection
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
Additional description: Gastrointestinal infection
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Implant site abscess
Additional description: Implant site abscess
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
Additional description: Infection
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
Additional description: Localised infection
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral candidiasis
Additional description: Oral candidiasis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	2 / 77 (2.60%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
Additional description: Postoperative wound infection
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
Additional description: Sepsis
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
Additional description: Viral infection
subjects affected / exposed	0 / 77 (0.00%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Electrolyte imbalance
Additional description: Electrolyte imbalance
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
Additional description: Hyperglycaemia
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	0 / 77 (0.00%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Chemotherapy conventional sequence with L-BLP25	Chemotherapy conventional sequence without L-BLP25	Chemotherapy reverse sequence with L-BLP25	Chemotherapy reverse sequence without L-BLP25	Endocrine Aromatase inhibitor therapy with L-BLP25	Endocrine Aromatase inhibitor therapy without L-BLP25
Total subjects affected by non serious adverse events
subjects affected / exposed	77 / 77 (100.00%)	77 / 77 (100.00%)	76 / 77 (98.70%)	78 / 78 (100.00%)	25 / 41 (60.98%)	25 / 46 (54.35%)
Vascular disorders
Flushing
Additional description: Flushing
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	5 / 77 (6.49%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	7	2	0	0
Hot flush
Additional description: Hot flush
subjects affected / exposed	14 / 77 (18.18%)	13 / 77 (16.88%)	18 / 77 (23.38%)	15 / 78 (19.23%)	5 / 41 (12.20%)	6 / 46 (13.04%)
occurrences all number	18	16	22	19	6	6
Thrombophlebitis
Additional description: Thrombophlebitis
subjects affected / exposed	10 / 77 (12.99%)	4 / 77 (5.19%)	5 / 77 (6.49%)	3 / 78 (3.85%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	13	4	5	5	0	0
General disorders and administration site conditions
Asthenia
Additional description: Asthenia
subjects affected / exposed	3 / 77 (3.90%)	7 / 77 (9.09%)	7 / 77 (9.09%)	3 / 78 (3.85%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	4	11	8	7	0	1
Axillary pain
Additional description: Axillary pain
subjects affected / exposed	4 / 77 (5.19%)	2 / 77 (2.60%)	3 / 77 (3.90%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	4	2	3	1	0	0
Chest pain
Additional description: Chest pain
subjects affected / exposed	3 / 77 (3.90%)	2 / 77 (2.60%)	3 / 77 (3.90%)	1 / 78 (1.28%)	3 / 41 (7.32%)	0 / 46 (0.00%)
occurrences all number	3	2	3	2	3	0
Fatigue
Additional description: Fatigue
subjects affected / exposed	54 / 77 (70.13%)	49 / 77 (63.64%)	45 / 77 (58.44%)	47 / 78 (60.26%)	6 / 41 (14.63%)	5 / 46 (10.87%)
occurrences all number	132	127	97	110	7	5
Injection site erythema
Additional description: Injection site erythema
subjects affected / exposed	4 / 77 (5.19%)	0 / 77 (0.00%)	9 / 77 (11.69%)	0 / 78 (0.00%)	4 / 41 (9.76%)	0 / 46 (0.00%)
occurrences all number	8	0	12	0	5	0
Mucosal dryness
Additional description: Mucosal dryness
subjects affected / exposed	9 / 77 (11.69%)	6 / 77 (7.79%)	8 / 77 (10.39%)	2 / 78 (2.56%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	10	9	8	3	1	0
Mucosal inflammation
Additional description: Mucosal inflammation
subjects affected / exposed	4 / 77 (5.19%)	6 / 77 (7.79%)	6 / 77 (7.79%)	7 / 78 (8.97%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	7	12	9	9	0	0
Oedema
Additional description: Oedema
subjects affected / exposed	0 / 77 (0.00%)	2 / 77 (2.60%)	6 / 77 (7.79%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	3	7	1	0	0
Oedema peripheral
Additional description: Oedema peripheral
subjects affected / exposed	19 / 77 (24.68%)	14 / 77 (18.18%)	20 / 77 (25.97%)	24 / 78 (30.77%)	1 / 41 (2.44%)	1 / 46 (2.17%)
occurrences all number	22	17	32	29	1	1
Pain
Additional description: Pain
subjects affected / exposed	10 / 77 (12.99%)	12 / 77 (15.58%)	7 / 77 (9.09%)	3 / 78 (3.85%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	16	20	10	4	0	0
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	17 / 77 (22.08%)	6 / 77 (7.79%)	7 / 77 (9.09%)	11 / 78 (14.10%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	21	6	8	14	0	1
Reproductive system and breast disorders
Breast pain
Additional description: Breast pain
subjects affected / exposed	3 / 77 (3.90%)	4 / 77 (5.19%)	5 / 77 (6.49%)	3 / 78 (3.85%)	2 / 41 (4.88%)	1 / 46 (2.17%)
occurrences all number	4	5	6	5	2	1
Menstruation irregular
Additional description: Menstruation irregular
subjects affected / exposed	0 / 77 (0.00%)	4 / 77 (5.19%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	4	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
Additional description: Cough
subjects affected / exposed	15 / 77 (19.48%)	10 / 77 (12.99%)	8 / 77 (10.39%)	5 / 78 (6.41%)	2 / 41 (4.88%)	3 / 46 (6.52%)
occurrences all number	18	10	9	5	3	5
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	5 / 77 (6.49%)	9 / 77 (11.69%)	7 / 77 (9.09%)	7 / 78 (8.97%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	11	12	12	0	0
Dyspnoea exertional
Additional description: Dyspnoea exertional
subjects affected / exposed	0 / 77 (0.00%)	1 / 77 (1.30%)	2 / 77 (2.60%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	0	1	3	5	0	0
Epistaxis
Additional description: Epistaxis
subjects affected / exposed	4 / 77 (5.19%)	3 / 77 (3.90%)	9 / 77 (11.69%)	5 / 78 (6.41%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	5	4	12	5	0	0
Oropharyngeal pain
Additional description: Oropharyngeal pain
subjects affected / exposed	14 / 77 (18.18%)	7 / 77 (9.09%)	12 / 77 (15.58%)	8 / 78 (10.26%)	0 / 41 (0.00%)	2 / 46 (4.35%)
occurrences all number	19	7	20	10	0	2
Psychiatric disorders
Insomnia
Additional description: Insomnia
subjects affected / exposed	4 / 77 (5.19%)	7 / 77 (9.09%)	9 / 77 (11.69%)	8 / 78 (10.26%)	1 / 41 (2.44%)	3 / 46 (6.52%)
occurrences all number	5	10	10	11	1	3
Sleep disorder
Additional description: Sleep disorder
subjects affected / exposed	8 / 77 (10.39%)	10 / 77 (12.99%)	11 / 77 (14.29%)	12 / 78 (15.38%)	6 / 41 (14.63%)	4 / 46 (8.70%)
occurrences all number	9	10	11	13	6	4
Investigations
Body temperature increased
Additional description: Body temperature increased
subjects affected / exposed	4 / 77 (5.19%)	1 / 77 (1.30%)	5 / 77 (6.49%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	1	6	5	0	0
Injury, poisoning and procedural complications
Procedural pain
Additional description: Procedural pain
subjects affected / exposed	2 / 77 (2.60%)	4 / 77 (5.19%)	3 / 77 (3.90%)	4 / 78 (5.13%)	2 / 41 (4.88%)	1 / 46 (2.17%)
occurrences all number	2	5	3	4	2	1
Seroma
Additional description: Seroma
subjects affected / exposed	3 / 77 (3.90%)	5 / 77 (6.49%)	3 / 77 (3.90%)	5 / 78 (6.41%)	1 / 41 (2.44%)	1 / 46 (2.17%)
occurrences all number	3	5	3	5	1	1
Cardiac disorders
Cardiovascular disorder
Additional description: Cardiovascular disorder
subjects affected / exposed	4 / 77 (5.19%)	3 / 77 (3.90%)	2 / 77 (2.60%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	4	3	2	1	0	0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	5 / 77 (6.49%)	5 / 77 (6.49%)	6 / 77 (7.79%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	7	9	9	5	0	0
Nervous system disorders
Ageusia
Additional description: Ageusia
subjects affected / exposed	2 / 77 (2.60%)	0 / 77 (0.00%)	1 / 77 (1.30%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	0	1	7	0	0
Dysgeusia
Additional description: Dysgeusia
subjects affected / exposed	19 / 77 (24.68%)	23 / 77 (29.87%)	25 / 77 (32.47%)	30 / 78 (38.46%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	24	27	35	45	1	0
Headache
Additional description: Headache
subjects affected / exposed	22 / 77 (28.57%)	18 / 77 (23.38%)	23 / 77 (29.87%)	13 / 78 (16.67%)	4 / 41 (9.76%)	3 / 46 (6.52%)
occurrences all number	29	23	30	20	4	4
Hypoaesthesia
Additional description: Hypoaesthesia
subjects affected / exposed	3 / 77 (3.90%)	2 / 77 (2.60%)	7 / 77 (9.09%)	6 / 78 (7.69%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	3	2	12	9	0	0
Neuropathy peripheral
Additional description: Neuropathy peripheral
subjects affected / exposed	5 / 77 (6.49%)	8 / 77 (10.39%)	5 / 77 (6.49%)	4 / 78 (5.13%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	7	10	8	6	0	1
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	10 / 77 (12.99%)	9 / 77 (11.69%)	9 / 77 (11.69%)	15 / 78 (19.23%)	1 / 41 (2.44%)	1 / 46 (2.17%)
occurrences all number	16	13	17	23	1	1
Peripheral sensory neuropathy
Additional description: Peripheral sensory neuropathy
subjects affected / exposed	5 / 77 (6.49%)	3 / 77 (3.90%)	3 / 77 (3.90%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	3	4	3	0	0
Polyneuropathy
Additional description: Polyneuropathy
subjects affected / exposed	19 / 77 (24.68%)	20 / 77 (25.97%)	17 / 77 (22.08%)	14 / 78 (17.95%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	28	26	31	18	0	0
Tremor
Additional description: Tremor
subjects affected / exposed	5 / 77 (6.49%)	1 / 77 (1.30%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	5	2	2	0	0	0
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	9 / 77 (11.69%)	17 / 77 (22.08%)	9 / 77 (11.69%)	13 / 78 (16.67%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	17	35	17	27	0	0
Leukopenia
Additional description: Leukopenia
subjects affected / exposed	23 / 77 (29.87%)	25 / 77 (32.47%)	17 / 77 (22.08%)	15 / 78 (19.23%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	128	139	86	90	0	0
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	24 / 77 (31.17%)	24 / 77 (31.17%)	24 / 77 (31.17%)	17 / 78 (21.79%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	92	103	69	87	0	0
Ear and labyrinth disorders
Tinnitus
Additional description: Tinnitus
subjects affected / exposed	2 / 77 (2.60%)	0 / 77 (0.00%)	4 / 77 (5.19%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	0	5	0	0	0
Vertigo
Additional description: Vertigo
subjects affected / exposed	12 / 77 (15.58%)	10 / 77 (12.99%)	17 / 77 (22.08%)	7 / 78 (8.97%)	2 / 41 (4.88%)	1 / 46 (2.17%)
occurrences all number	20	14	27	7	2	1
Eye disorders
Conjunctivitis
Additional description: Conjunctivitis
subjects affected / exposed	2 / 77 (2.60%)	1 / 77 (1.30%)	4 / 77 (5.19%)	2 / 78 (2.56%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	3	2	6	4	1	0
Dry eye
Additional description: Dry eye
subjects affected / exposed	5 / 77 (6.49%)	3 / 77 (3.90%)	5 / 77 (6.49%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	5	4	5	4	0	0
Lacrimation increased
Additional description: Lacrimation increased
subjects affected / exposed	8 / 77 (10.39%)	17 / 77 (22.08%)	18 / 77 (23.38%)	15 / 78 (19.23%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	9	21	21	17	0	0
Visual acuity reduced
Additional description: Visual acuity reduced
subjects affected / exposed	1 / 77 (1.30%)	5 / 77 (6.49%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	5	0	1	0	0
Gastrointestinal disorders
Abdominal discomfort
Additional description: Abdominal discomfort
subjects affected / exposed	3 / 77 (3.90%)	0 / 77 (0.00%)	5 / 77 (6.49%)	4 / 78 (5.13%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	4	0	6	6	0	1
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	4 / 77 (5.19%)	2 / 77 (2.60%)	5 / 77 (6.49%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	5	4	5	4	0	0
Abdominal pain upper
Additional description: Abdominal pain upper
subjects affected / exposed	5 / 77 (6.49%)	7 / 77 (9.09%)	8 / 77 (10.39%)	6 / 78 (7.69%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	7	9	6	0	0
Constipation
Additional description: Constipation
subjects affected / exposed	27 / 77 (35.06%)	27 / 77 (35.06%)	27 / 77 (35.06%)	30 / 78 (38.46%)	2 / 41 (4.88%)	2 / 46 (4.35%)
occurrences all number	46	46	47	51	2	2
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	16 / 77 (20.78%)	21 / 77 (27.27%)	29 / 77 (37.66%)	29 / 78 (37.18%)	4 / 41 (9.76%)	0 / 46 (0.00%)
occurrences all number	28	35	48	39	5	0
Dry mouth
Additional description: Dry mouth
subjects affected / exposed	6 / 77 (7.79%)	6 / 77 (7.79%)	2 / 77 (2.60%)	1 / 78 (1.28%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	6	6	2	1	0	1
Dyspepsia
Additional description: Dyspepsia
subjects affected / exposed	6 / 77 (7.79%)	6 / 77 (7.79%)	7 / 77 (9.09%)	5 / 78 (6.41%)	1 / 41 (2.44%)	1 / 46 (2.17%)
occurrences all number	6	9	9	5	1	1
Dysphagia
Additional description: Dysphagia
subjects affected / exposed	1 / 77 (1.30%)	3 / 77 (3.90%)	4 / 77 (5.19%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	1	4	4	0	0	0
Flatulence
Additional description: Flatulence
subjects affected / exposed	2 / 77 (2.60%)	4 / 77 (5.19%)	0 / 77 (0.00%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	4	0	1	0	0
Gastrooesophageal reflux disease
Additional description: Gastrooesophageal reflux disease
subjects affected / exposed	6 / 77 (7.79%)	5 / 77 (6.49%)	3 / 77 (3.90%)	3 / 78 (3.85%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	8	3	3	0	0
Haemorrhoids
Additional description: Haemorrhoids
subjects affected / exposed	4 / 77 (5.19%)	1 / 77 (1.30%)	2 / 77 (2.60%)	1 / 78 (1.28%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	4	1	2	1	1	0
Nausea
Additional description: Nausea
subjects affected / exposed	57 / 77 (74.03%)	51 / 77 (66.23%)	50 / 77 (64.94%)	41 / 78 (52.56%)	6 / 41 (14.63%)	0 / 46 (0.00%)
occurrences all number	114	101	108	71	7	0
Stomatitis
Additional description: Stomatitis
subjects affected / exposed	24 / 77 (31.17%)	15 / 77 (19.48%)	16 / 77 (20.78%)	18 / 78 (23.08%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	41	29	40	29	0	0
Vomiting
Additional description: Vomiting
subjects affected / exposed	16 / 77 (20.78%)	14 / 77 (18.18%)	6 / 77 (7.79%)	9 / 78 (11.54%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	23	16	8	10	1	0
Skin and subcutaneous tissue disorders
Acne
Additional description: Acne
subjects affected / exposed	1 / 77 (1.30%)	0 / 77 (0.00%)	4 / 77 (5.19%)	1 / 78 (1.28%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	0	5	2	0	0
Alopecia
Additional description: Alopecia
subjects affected / exposed	33 / 77 (42.86%)	38 / 77 (49.35%)	32 / 77 (41.56%)	31 / 78 (39.74%)	1 / 41 (2.44%)	3 / 46 (6.52%)
occurrences all number	38	41	35	34	1	3
Dry skin
Additional description: Dry skin
subjects affected / exposed	7 / 77 (9.09%)	9 / 77 (11.69%)	14 / 77 (18.18%)	8 / 78 (10.26%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	8	9	15	9	0	1
Erythema
Additional description: Erythema
subjects affected / exposed	5 / 77 (6.49%)	6 / 77 (7.79%)	11 / 77 (14.29%)	5 / 78 (6.41%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	6	11	14	5	1	0
Hyperhidrosis
Additional description: Hyperhidrosis
subjects affected / exposed	5 / 77 (6.49%)	5 / 77 (6.49%)	4 / 77 (5.19%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	5	4	2	0	0
Nail discolouration
Additional description: Nail discolouration
subjects affected / exposed	6 / 77 (7.79%)	2 / 77 (2.60%)	2 / 77 (2.60%)	5 / 78 (6.41%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	6	2	2	5	0	0
Nail disorder
Additional description: Nail disorder
subjects affected / exposed	9 / 77 (11.69%)	6 / 77 (7.79%)	14 / 77 (18.18%)	13 / 78 (16.67%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	9	7	17	13	0	0
Nail dystrophy
Additional description: Nail dystrophy
subjects affected / exposed	6 / 77 (7.79%)	3 / 77 (3.90%)	5 / 77 (6.49%)	3 / 78 (3.85%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	7	3	5	3	0	0
Onychalgia
Additional description: Onychalgia
subjects affected / exposed	2 / 77 (2.60%)	1 / 77 (1.30%)	2 / 77 (2.60%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	1	3	5	0	0
Onychoclasis
Additional description: Onychoclasis
subjects affected / exposed	3 / 77 (3.90%)	4 / 77 (5.19%)	10 / 77 (12.99%)	7 / 78 (8.97%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	3	4	10	7	0	0
Palmar-plantar erythrodysaesthesia syndrome
Additional description: Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	2 / 77 (2.60%)	6 / 77 (7.79%)	4 / 77 (5.19%)	3 / 78 (3.85%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	4	12	4	3	0	0
Pruritus
Additional description: Pruritus
subjects affected / exposed	3 / 77 (3.90%)	3 / 77 (3.90%)	8 / 77 (10.39%)	5 / 78 (6.41%)	2 / 41 (4.88%)	1 / 46 (2.17%)
occurrences all number	3	3	9	5	2	2
Rash
Additional description: Rash
subjects affected / exposed	4 / 77 (5.19%)	4 / 77 (5.19%)	18 / 77 (23.38%)	14 / 78 (17.95%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	5	4	23	15	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: Arthralgia
subjects affected / exposed	9 / 77 (11.69%)	16 / 77 (20.78%)	11 / 77 (14.29%)	17 / 78 (21.79%)	6 / 41 (14.63%)	9 / 46 (19.57%)
occurrences all number	14	20	13	23	7	11
Back pain
Additional description: Back pain
subjects affected / exposed	4 / 77 (5.19%)	1 / 77 (1.30%)	3 / 77 (3.90%)	4 / 78 (5.13%)	1 / 41 (2.44%)	2 / 46 (4.35%)
occurrences all number	4	1	3	7	1	2
Bone pain
Additional description: Bone pain
subjects affected / exposed	24 / 77 (31.17%)	24 / 77 (31.17%)	19 / 77 (24.68%)	28 / 78 (35.90%)	1 / 41 (2.44%)	1 / 46 (2.17%)
occurrences all number	37	40	32	58	1	2
Muscle spasms
Additional description: Muscle spasms
subjects affected / exposed	1 / 77 (1.30%)	4 / 77 (5.19%)	1 / 77 (1.30%)	1 / 78 (1.28%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	1	4	1	1	0	1
Musculoskeletal pain
Additional description: Musculoskeletal pain
subjects affected / exposed	4 / 77 (5.19%)	2 / 77 (2.60%)	4 / 77 (5.19%)	5 / 78 (6.41%)	4 / 41 (9.76%)	1 / 46 (2.17%)
occurrences all number	4	2	4	9	4	2
Myalgia
Additional description: Myalgia
subjects affected / exposed	17 / 77 (22.08%)	18 / 77 (23.38%)	21 / 77 (27.27%)	17 / 78 (21.79%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	28	23	35	23	0	0
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	17 / 77 (22.08%)	16 / 77 (20.78%)	17 / 77 (22.08%)	18 / 78 (23.08%)	0 / 41 (0.00%)	1 / 46 (2.17%)
occurrences all number	27	22	27	25	0	1
Infections and infestations
Infection
Additional description: Infection
subjects affected / exposed	5 / 77 (6.49%)	1 / 77 (1.30%)	3 / 77 (3.90%)	0 / 78 (0.00%)	1 / 41 (2.44%)	0 / 46 (0.00%)
occurrences all number	6	1	3	0	1	0
Nasopharyngitis
Additional description: Nasopharyngitis
subjects affected / exposed	16 / 77 (20.78%)	13 / 77 (16.88%)	8 / 77 (10.39%)	10 / 78 (12.82%)	2 / 41 (4.88%)	2 / 46 (4.35%)
occurrences all number	17	15	9	13	2	2
Oral candidiasis
Additional description: Oral candidiasis
subjects affected / exposed	7 / 77 (9.09%)	8 / 77 (10.39%)	10 / 77 (12.99%)	9 / 78 (11.54%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	16	13	17	14	0	0
Oral herpes
Additional description: Oral herpes
subjects affected / exposed	8 / 77 (10.39%)	4 / 77 (5.19%)	2 / 77 (2.60%)	2 / 78 (2.56%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	8	4	2	2	0	0
Pharyngitis
Additional description: Pharyngitis
subjects affected / exposed	2 / 77 (2.60%)	3 / 77 (3.90%)	2 / 77 (2.60%)	6 / 78 (7.69%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	2	3	2	6	0	0
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	5 / 77 (6.49%)	6 / 77 (7.79%)	4 / 77 (5.19%)	4 / 78 (5.13%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	5	6	5	4	0	0
Rhinitis
Additional description: Rhinitis
subjects affected / exposed	5 / 77 (6.49%)	8 / 77 (10.39%)	8 / 77 (10.39%)	7 / 78 (8.97%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	7	9	8	7	0	0
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	7 / 77 (9.09%)	7 / 77 (9.09%)	5 / 77 (6.49%)	5 / 78 (6.41%)	3 / 41 (7.32%)	4 / 46 (8.70%)
occurrences all number	11	7	8	7	4	4
Metabolism and nutrition disorders
Decreased appetite
Additional description: Decreased appetite
subjects affected / exposed	7 / 77 (9.09%)	13 / 77 (16.88%)	14 / 77 (18.18%)	12 / 78 (15.38%)	3 / 41 (7.32%)	0 / 46 (0.00%)
occurrences all number	7	16	16	14	3	0
Increased appetite
Additional description: Increased appetite
subjects affected / exposed	4 / 77 (5.19%)	0 / 77 (0.00%)	1 / 77 (1.30%)	0 / 78 (0.00%)	0 / 41 (0.00%)	0 / 46 (0.00%)
occurrences all number	4	0	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

20 Sep 2013

Main changes included updates on subset of patients for safety run in phase, on parameters for early stopping rule, estimated treatment and study duration, details for L-BLP25 treatment and non-investigational medicinal products, requirements for DMC requests, definition of time windows for study assessments, and definition of interim analysis

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.

None reported

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Clinical trials

Clinical Trial Results: A prospective, open, randomized, phase-II study of a therapeutic cancer vaccine (L-BLP25, Stimuvax®) in the pre-operative treatment of women with primary breast cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Residual Cancer Burden (RCB)

Primary: Residual Cancer Burden (RCB)

Secondary: Pathological Complete Response (pCR)

Secondary: Pathological Complete Response (pCR)

Secondary: Residual Cancer Burden (RCB) - conv vs rev

Secondary: Residual Cancer Burden (RCB) - conv vs rev

Secondary: Tumor Associated Lymphocytes (TAL) - stromal BL

Secondary: Tumor Associated Lymphocytes (TAL) - stromal BL

Secondary: Tumor Associated Lymphocytes (TAL) - stromal MT

Secondary: Tumor Associated Lymphocytes (TAL) - stromal MT

Secondary: Tumor Associated Lymphocytes (TAL) - stromal SU

Secondary: Tumor Associated Lymphocytes (TAL) - stromal SU

Secondary: Change in Tumor Associated Lymphocytes (TAL) - stromal BL to MT

Secondary: Change in Tumor Associated Lymphocytes (TAL) - stromal BL to MT

Secondary: Change in Tumor Associated Lymphocytes (TAL) - stromal BL to SU

Secondary: Change in Tumor Associated Lymphocytes (TAL) - stromal BL to SU

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral BL

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral BL

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral MT

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral MT

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral SU

Secondary: Tumor Associated Lymphocytes (TAL) - intratumoral SU

Secondary: Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to MT

Secondary: Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to MT

Secondary: Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to SU

Secondary: Change in Tumor Associated Lymphocytes (TAL) - intratumoral BL to SU

Secondary: Ki67 tumor status (MIB1) - BL

Secondary: Ki67 tumor status (MIB1) - BL

Secondary: Ki67 tumor status (MIB1) - MT

Secondary: Ki67 tumor status (MIB1) - MT

Secondary: Ki67 tumor status (MIB1) - SU

Secondary: Ki67 tumor status (MIB1) - SU

Secondary: Change in Ki67 tumor status (MIB1) - BL to MT

Secondary: Change in Ki67 tumor status (MIB1) - BL to MT

Secondary: Change in Ki67 tumor status (MIB1) - BL to SU

Secondary: Change in Ki67 tumor status (MIB1) - BL to SU

Secondary: Change in Quality of Life (QoL) - BL to SU

Secondary: Change in Quality of Life (QoL) - BL to SU

Secondary: Change in Quality of Life (QoL) - BL to EOS

Secondary: Change in Quality of Life (QoL) - BL to EOS

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A prospective, open, randomized, phase-II study of a therapeutic cancer vaccine (L-BLP25, Stimuvax®) in the pre-operative treatment of women with primary breast cancer