Impact of Dermatological Toxicities on Quality of Life in Patients With Early Breast Cancer Exposed to Adjuvant Endocrine Therapy: a Real-world Cross-sectional Study. BCARE (Breast Cancer Adjuvant Real-world Evaluation of Dermatological Adverse Events)
Conditions: Early Breast Cancer, Skin Condition, Quality of Life
Sponsor: Pierre Fabre Medicament

 
 
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BCARE (Breast Cancer Adjuvant Real-world Evaluation 
of Dermatological adverse events) 
 
 
 
 
 
 
 
 
 
 
 
Version 3.0 - Date 23 May 2025 
 
Sponsor  
PIERRE FABRE MEDICAMENT 
Protocol number  
NIS18999 
NCT Number 
NCT06690489 
 
 

 
 
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HISTORY OF CHANGES 
Protocol N° 
Date 
Countries involved 
Main changes 
Amended protocol 3.0 
23 May 2025 
All 
Modification of the inclusion 
criterion #3 and addition of an 
interim analysis in order to 
communicate preliminary results 
to congress. 
Amended protocol 2.0 
04 November 2024 
All 
Updated as all PROs were finally 
available in Greek and could be 
completed by Greek patients. 
Initial 1.0 
05 July 2024 
All 
 
 
SUMMARY OF CHANGES 
 
Summary of changes from version 2.0 dated 4 November 2024 to version 3.0 dated 23 May 2025 
Section # and Name 
Description of Change 
Brief Rationale  
Sections 1 Synopsis
(inclusion 
and 
exclusion criteria) and 
4.2.1.1 
Inclusion 
criteria as well as any 
section where the time 
 
Modification of the inclusion criterion #3. The 
sentence: 
Still being treated with adjuvant 
endocrine monotherapy, initiated 2 to 3 years 
ago before the inclusion in the study  
Still being treated with adjuvant 
endocrine monotherapy, initiated 2 years (up to 
1 year and 9 months) to 3 years (up to 3 years 
and 6 months) before the inclusion in the study.
The modification of inclusion 
criterion #3 aims to introduce a 
more accurate and flexible time 
window for initiation of adjuvant 
endocrine 
therapy, 
allowing 
inclusion of patients treated for 2 
years (up to 1 year and 9 months)
to 3 years (up to 3 years and 6 
months) prior to study inclusion. 
This 
will 
help 
with 
the 
identification of eligible patients 
in a real-world setting.  
Section 4.7.8 Interim 
analysis 
This section has been added due to the addition 
of an interim analysis on Q2-Q3 2025. 
An interim analysis will be 
performed 
to 
communicate 
preliminary results to congress. 
Section 7 Plans for 
disseminating 
and 
communicating 
study 
results 
The following sentence has been added: Of 
note, no clinical study report will be written for 
the interim analysis.  
This sentence has been added for 
clarification due to the addition of 
an interim analysis. 
 
 

 
 
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TABLE OF CONTENTS 
 
HISTORY OF CHANGES ........................................................................................................................... 2 
SUMMARY OF CHANGES ........................................................................................................................ 2 
TABLE OF CONTENTS .............................................................................................................................. 3 
LIST OF ABBREVIATIONS ....................................................................................................................... 6 
1 
SYNOPSIS ............................................................................................................................................. 7 
2 
BACKGROUND AND RATIONALE .............................................................................................. 13 
2.1 
BACKGROUND ............................................................................................................. 13 
2.2 
RATIONALE .................................................................................................................. 16 
3 
STUDY OBJECTIVES ...................................................................................................................... 18 
3.1 
PRIMARY OBJECTIVE ................................................................................................. 18 
3.2 
SECONDARY OBJECTIVES ........................................................................................ 18 
3.3 
EXPLORATORY OBJECTIVES ................................................................................... 18 
4 
RESEARCH METHODS................................................................................................................... 19 
4.1 
STUDY DESIGN ............................................................................................................ 19 
4.2 
POPULATIONS .............................................................................................................. 20 
4.2.1 
Study population ...................................................................................................... 20 
4.2.2 
Patient selection ...................................................................................................... 21 
4.3 
STUDY OUTCOMES ..................................................................................................... 22 
4.3.1 
Primary outcome ..................................................................................................... 22 
4.3.2 
Secondary outcomes ................................................................................................ 23 
4.3.3 
Exploratory outcomes .............................................................................................. 24 
4.3.4 
Subgroups of interest ............................................................................................... 24 
4.4 
DATA SOURCES ........................................................................................................... 25 
4.5 
STUDY SIZE .................................................................................................................. 25 
4.6 
DATA MANAGEMENT ................................................................................................ 25 
4.7 
DATA ANALYSIS ......................................................................................................... 27 
4.7.1 
General considerations ........................................................................................... 27 
4.7.2 
Data-set definition ................................................................................................... 27 
4.7.3 
Analysis of primary outcomes ................................................................................. 27 
4.7.4 
Analysis of secondary outcomes .............................................................................. 27 
4.7.5 
Analysis of exploratory outcomes ............................................................................ 28 
4.7.6 
Missing data ............................................................................................................ 28 
4.7.7 
Interim analysis ....................................................................................................... 28 
4.8 
QUALITY CONTROL .................................................................................................... 28 
4.9 
STUDY MANAGEMENT .............................................................................................. 29 
4.10 
LIMITATIONS OF THE RESEARCH METHODS ....................................................... 30 
5 
PROTECTION OF HUMAN SUBJECTS AND LOCAL REGULATORY ASPECTS .............. 32 
6 
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS ..... 33 
7 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS ..................... 34 

 
 
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8 
OWNERSHIP OF RESULTS ............................................................................................................ 35 
9 
REFERENCES ................................................................................................................................... 36 
10 
APPENDICES ..................................................................................................................................... 40 
10.1 
SIGNATURE PAGES ........................................................................................................... 40 
10.2 
QUESTIONNAIRES ............................................................................................................. 43 
10.2.1 
DLQI questionnaire - 2019 ..................................................................................... 43 
10.2.2 
Skindex-16 questionnaire  2001 ............................................................................ 44 
10.2.3 
Hairdex questionnaire  version 2010 .................................................................... 46 
10.2.4 
ItchyQoL questionnaire  Version 2012 ................................................................. 49 
 
 
 

 
 
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LIST OF FIGURES 
 
Figure 1 - Early breast cancer treatment algorithm according to ESMO (Cardoso, 2019). ............ 14 
 
 
 

 
 
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LIST OF ABBREVIATIONS 
 
BCARE 
Breast Cancer Adjuvant Real-world Evaluation of Dermatological adverse 
events 
BCS 
Breast-Conserving Surgery 
ChT 
Chemotherapy 
CI 
Confidence Interval 
CTCAE 
Common Terminology Criteria for Adverse Events 
CRO 
Contract Research Organization 
DLQI 
Dermatology Life Quality Index 
EADV 
European Academy of Dermatology and Venereology - European Task Force 
EBC 
Early Breast Cancer 
eCRF 
ePRO 
electronic Case Report Form 
electronic Patient Reported Outcome 
EMA 
European Medicine Agency 
ER 
Estrogen Receptor 
ESMO 
European Society for Medical Oncology 
GCP 
Good Clinical Practice 
GVP 
Good Pharmacovigilance Practice 
HER2 
Human Epidermal growth factor Receptor 2 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonization 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
MRI 
Magnetic Resonance Imaging 
PgR 
Progesterone Receptor 
QC 
Quality Control 
QoL 
Quality Of Life 
RT 
Radiotherapy 
SAP 
Statistical Analysis Plan 
TNBC 
Triple-Negative Breast Cancer 
TNM 
Tumor Node Metastasis 
WHO 
World Health Organization 
 
 

 
 
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1 
SYNOPSIS 
STUDY TITLE 
Impact of dermatological toxicities on quality of life in patients with early 
breast cancer exposed to adjuvant endocrine therapy: a real-world cross-
sectional study. 
BCARE (Breast Cancer Adjuvant Real-world Evaluation of Dermatological 
adverse events) 
SPONSOR 
PIERRE FABRE MEDICAMENT 
STUDY 
RATIONALE 
Dermatological toxicities are among the most common adverse events 
experienced by patients treated with anti-cancer therapies. With improved 
efficacy of anticancer treatments, cancer patients are living longer and report 
a better quality of life; however dermatological toxicities, such as skin 
inflammation, hair/nail changes, facial flushing, erythema or dry skin are still 
and social well-being. For these patients, the initiation of a skin care 
management is crucial to improve quality of life and ensure compliance to 
treatment. It has been confirmed that adverse events of endocrine therapy are 
significantly associated with anxiety and depression.  
Very few studies explored the quality of life related to dermatological
toxicities of breast cancer patients exposed to endocrine therapy for a 
prolonged period. The use of endocrine agents is associated with frequent 
dermatological toxicities, including skin lesions, oral symptoms, nail changes 
or alopecia. Besides quality-of-life impairment of cancer patients, these 
reactions can lead to treatment adjustment or interruption. As patients live 
longer on cancer therapies, there is a need to identify factors of clinically 
significant events and to develop improved and widely available preventive 
strategies, all of which would contribute to the optimal and comprehensive 
care of cancer patients. 
Dermatological toxicities induced by adjuvant endocrine therapy can have a 
negative 
has been
exceptionally described in literature. To improve the QoL of patients treated 
with adjuvant endocrine therapy, a comprehensive understanding of the 
ongoing impact of these dermatological toxicities is lacking. 
This transversal study aims to describe the dermatological toxicities reported 
by European patients with early breast cancer treated with adjuvant endocrine 
therapy. This study will describe specifically the impact on quality of life 
related to dermatological toxicities of this population. 
To avoid catching dermatological toxicities related to prior treatments, only 
early breast cancer in female patients, currently treated with adjuvant 

 
 
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endocrine monotherapy initiated 2 years (up to 1 year and 9 months) to 3 
years (up to 3 years and 6 months) before the present study, will be included.
STUDY 
OBJECTIVES 
Primary objective 
To measure the quality of life related to dermatological toxicities, using 
Dermatology Life Quality Index (DLQI) questionnaire, in female patients 
with early breast cancer (defined according to World Health Organization 
[WHO] classification and the 8th edition of the American Joint Committee on 
Cancer tumor, node, metastasis [TNM] staging system) being treated with 
ongoing adjuvant endocrine therapy in monotherapy, initiated 2 years (up to 
1 year and 9 months) to 3 years (up to 3 years and 6 months) before inclusion 
in the study. 
Secondary objectives 
Secondary objectives aim, in female patients with early breast cancer (EBC), 
being treated with ongoing adjuvant endocrine monotherapy initiated 2 years 
(up to 1 year and 9 months) to 3 years (up to 3 years and 6 months) before 
inclusion in the study, to describe: 
1. The dermatological quality, using Skindex-16, Hairdex, and 
ItchyQoL questionnaires. 
2. The real-world dermatological toxicities present at inclusion. 
3. The demographics characteristics, and the clinical characteristics. 
Exploratory objectives 
To describe real-world dermatological toxicities, from the beginning of their 
endocrine therapy to the time of data collection, of female patients with EBC,
being treated with ongoing adjuvant endocrine monotherapy initiated 2 years 
(up to 1 year and 9 months) to 3 years (up to 3 years and 6 months) before 
inclusion in the study. 
STUDY 
OUTCOMES 
Primary outcome  
Quality of life data collected at the time of inclusion using the validated DLQI
questionnaire. 
is calculated by summing the score of each question resulting in a maximum 
of 30 and a minimum of 0. The higher the score, the more quality of life is 
impaired: 0  1 corresponds to no effect at all on patient's life; 2  5 
corresponds to small effect on patient's life; 6  10 corresponds to moderate 
effect on patient's life; 11  20 corresponds to very large effect on patient's 
life; 21  30 corresponds to extremely large effect on patient's life. 

 
 
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Secondary outcomes 
1. Quality of life data collected at the time of inclusion using the 
Skindex-16, Hairdex, and ItchyQoL questionnaires. 
2. Ongoing dermatological toxicities reported by investigator according 
to Common Terminology Criteria for Adverse Events (CTCAE)
(version 5.0, November 2017): 
a. Type of toxicity 
b. Surface area involved (except for nails and oral dryness) 
c. Start date 
d. Clinical grading of the toxicity 
3. Demographics, and clinical characteristics at the time of inclusion, 
including the following items: 
a. Age, gender, weight, height 
b. Menopausal status 
c. Date of cancer diagnosis 
d. Primary tumor location 
e. T stage 
f. Prior therapies for breast cancer (type, agent name, start date, 
stop date) 
g. Endocrine therapy (agent name, start date) for breast cancer 
h. Current dermatological care and sun-protective behaviors 
Exploratory outcomes 
History of dermatological toxicities from the beginning of current treatment 
to the time of inclusion: 
a. Type of dermatological toxicity 
b. Surface area (except for nails and oral dryness) 
c. Start date and end date 
d. Grade of the toxicity, if available 

 
 
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e. Change in hormonal treatment (adaptation, interruption), if 
applicable. 
STUDY DESIGN European (including France, Greece, Italy, Spain), multicenter (from the 
EADV European Academy of Dermatology and Venereology - European 
Task Force D
), real world observational,
cross-sectional study, to describe the quality of life related to dermatological 
toxicities, in female patients with EBC, treated with ongoing adjuvant 
endocrine monotherapy initiated for 2 years (up to 1 year and 9 months) to 3 
years (up to 3 years and 6 months) before inclusion in the study. This is a 
cross-sectional, non-interventional study in which physicians and patients 
will follow local clinical practice. 
Patients will be asked to complete 4 questionnaires at the time of their 
inclusion. 
Medical 
history, 
demographics, 
clinical 
characteristics,
dermatological toxicities from the beginning of their endocrine therapy to the 
time of data collection will be collected from their medical charts. As this is 
a transversal study, there will not be any follow-up, and no safety data will 
be collected. 
STUDY 
POPULATION 
The study population will include approximately up to 156 patients with EBC
being treated with adjuvant endocrine monotherapy initiated 2 years (up to 1 
year and 9 months) and 3 years (up to 3 years and 6 months) before inclusion 
in the study. Participating sites will be encouraged to propose the study to all 
patients meeting the eligibility criteria, in a consecutive manner, when they 
come for consultation, in order to minimize bias in patient selection.  
INCLUSION 
AND 
EXCLUSION 
CRITERIA 
Inclusion criteria  
Patients will be eligible for inclusion if they fulfill ALL the following criteria:
1. Females a
. 
2. Histologically confirmed diagnosis of EBC, according to the WHO 
criteria and the TNM classification, at any time before inclusion. 
3. Still being treated with adjuvant endocrine monotherapy, initiated 2
years (up to 1 year and 9 months) to 3 years (up to 3 years and 6 
months) ago before the inclusion in the study. 
4. Signed Informed Consent Form (ICF) or non-opposition, according 
to local regulations. 
Exclusion criteria 

 
 
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Patients will not be eligible for inclusion if they fulfill ANY of the following 
criteria: 
1. Patients not able to read, understand and complete Questionnaires in 
local language. 
Exclusion criteria 
 
2. Patients with chronic dermatological conditions (treated or not)
before initiating the adjuvant endocrine therapy that could interfere 
with the quality of life. 
 Patients with concomitant targeted therapies with adjuvant endocrine 
therapy such as CDK4/6 inhibitors or trastuzumab, and patients with 
ongoing treatment with neratinib. 
3. Patients having relevant or severe comorbidities requiring complex 
therapeutic treatment. 
4. Patients having a persistent post-chemotherapy alopecia (at least of 
grade 1)  
SAMPLE SIZE  
Up to 156 patients to reach 140 evaluable patients. 
STATISTICS 
Sample size calculation 
Within this study, it is planned to recruit 156 patients. 
Accrual of 140 evaluable patients permits to estimate a 95% confidence 
interval of a proportion equals to 40% with an accuracy of +/-8%. The 
following table presents the accuracy for different proportions:  
 
Proportion of DLQI score 
6 
 
10% 
20% 
30% 
40% 
Accuracy (%) 
+/-5 
+/-6.5 
+/-7.5 
+/-8 
Assuming a rate of around 10% of non-evaluable patients (missing data), 156
patients will be included to reach 140 evaluable patients. 
Statistical analyses 
Statistical analyses will be fully described in a written Statistical Analysis 
Plan (SAP). The study endpoints will be analyzed overall and by predefined 
subgroup(s) of interest. Analyses will be descriptive in nature, as no 
hypothesis will be tested. In general, missing data will not be imputed (except 
for dates) and the data will be analyzed according to the complete case 
approach. 

 
 
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As regard to the descriptive nature of this study, an interim analysis will be 
performed on the patients included in the study coordinator
 (France) 
until the 15th of May 2025 in order to communicate preliminary results to 
congress. 
 
The demographic and clinical characteristics will be described using 
summary statistics. Categorical variables will be summarized by frequencies 
and percentages. Continuous variables will be summarized by descriptive 
statistics (mean, and standard deviation, median, 25th and 75th percentiles, 
minimum and maximum). The number of missing observations for each 
variable will also be reported.  

 
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2 
BACKGROUND AND RATIONALE 
2.1 
BACKGROUND 
In 2020, about 2.3 million new cases of breast cancer were diagnosed worldwide, accounting for 
almost one in four cancer cases among women, and nearly 30% died of it according to European 
Society for Medical Oncology (ESMO) (Loibl, 2024). The predicted number of new breast cancers 
in 28 European Union countries was 404 920, with estimated age-adjusted annual incidence of 
breast cancer of 144.9/100 000 and mortality of 32.9/100 000 (Dafani, 2019). About a quarter of 
breast cancers occurred before age 50, and less than 5% before age 35 (Cardoso, 2019). In 2018, 
ten-year survival of breast cancer exceeds 70% in most European regions, with 89% survival for 
local and 62% for regional disease (Cardoso, 2019; Nardin, 2020). The annual hazard of 
recurrence peaks in the second year after diagnosis but remains at 2% 5% in years 5 20 (Cardoso, 
2019). 
 
Diagnostic of primary tumor of breast cancer is obtained thanks to physical examination, 
mammography, breast ultrasound, breast Magnetic Resonance Imaging (MRI), and core biopsy 
with pathology determination of histology grade, estrogen receptor (ER), progesterone receptor 
(PgR), human epidermal growth factor receptor 2 (HER)2 and a proliferation marker, Ki67 
(Cardoso, 2019). Final pathological diagnosis should be made according to the World Health 
Organization (WHO) classification (Lakhani, 2012; Cardoso, 2019; Tan, 2020), and the eighth 
edition of the American Joint Committee on Cancer tumor, node, metastasis (TNM) staging system 
(Teichgraeber, 2021). 
arly Breast Cancer (EBC) is defined by the European Society for Medical Oncology 
(ESMO) (Loibl, 2024) as a stage where the tumor is 20 mm or smaller and has not spread to more 
than 3 lymph nodes. Alternatively, if the tumor is 20 to 50 mm in size and has not spread to any 
lymph nodes, it is also considered early-stage breast cancer. According to the European guidelines 
published by ESMO, the following decision tree for early breast cancer should be followed (see 
Figure 1 hereafter):  
 
 
 

 
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Figure 1 - Early breast cancer treatment algorithm according to ESMO (Cardoso, 2019). 
 
 
 
BCS, breast-conserving surgery; ChT, chemotherapy; ET, endocrine therapy; HER2, human epidermal growth factor 
receptor 2; RT, radiotherapy, TNBC, triple-negative breast cancer. 
aBiology that requires chemotherapy (TNBC, HER2-positive, luminal B-like), to assess response and prognosis and 
eventually decide on postoperative therapies, should preferentially receive preoperative chemotherapy. 
bAggressive phenotypes: TNBC or HER2-positive breast cancer. 
cIf chemotherapy is planned, it should all be given as neoadjuvant. 
dConcomitant postoperative radiotherapy, postoperative endocrine therapy and anti-HER2 therapy. 
 
Depending on the phenotypes and the retrieved biomarkers, the chemotherapy w/o endocrine 
therapy (tamoxifen) w/o anti-ER2 agents such as trastuzumab ± pertuzumab are chosen according 
to ESMO (Cardoso, 2019). Adjuvant endocrine therapy is one of the most important treatments of 
hormone-receptor-positive breast cancer and includes selective estrogen receptor modulators such 
as tamoxifen, aromatase inhibitors, and luteinizing hormone-releasing hormone analogs (Madigan, 
2020; Rossi, 2021). Adjuvant systemic treatment should preferably start within 3 6 weeks after 
surgery and neoadjuvant systemic therapy should start as soon as diagnosis and staging are 
completed (ideally within 2 4 weeks) (Cardoso, 2019).  

 
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Endocrine therapy should be used in all luminal-like cancers according to ESMO (Cardoso, 2019).  
For premenopausal women, tamoxifen for 5 10 years is a standard of care (Cardoso, 2019).  
 
Breast cancer is associated with adverse events related to depression, anxiety, chronic fatigue, sleep 
problems, joint symptoms, pain, sexual dysfunction, genitourinary syndrome of menopause and 
sleep disorders (Alnaim, 2022; Chan, 2020; Galvano, 2019; Lubián, 2022; Merlino, 2023; 
Roberts, 2022). Besides the systemic reactions (dyslipidemia, weight changes and bone mineral 
density modifications), local reactions such as dermatological toxicities including skin 
inflammation, hair/nail changes, facial flushing (hot flushes), erythema or dry skin due to cancer 
treatments 
and social well-being (Diana, 2021; Ferreira, 2019; Fessele, 2022; Lacouture, 2008; Lacouture, 
2021; Wagner, 2007). 
 
Hair changes (hair thinning and alopecia) is a common adverse event (overall incidence of 4.4%; 
and highest incidence of 25% with tamoxifen in a phase II trial) as reported in a larger study of a 
cohort, 19,430 patients with endocrine-related cancers in 35 clinical trials (Dell'Acqua, 2020). 
Although the alopecia is not severe, alopecia-related quality of life is deeply affected as the Hairdex 
questionnaire is reported to be 25.6, with a higher negative impact on emotions (Rossi, 2021).  
 
Common impact on skin such as rash, erythema or dry skin (23.66%) were also reported in 79 trials 
comparing 8669 patients receiving trastuzumab versus 9556 receiving no trastuzumab (Jackson, 
2022). Hot flushes are also reported as a common event (Cavadias, 2020; Peddie, 2021).  
The importance of the quality of life was highlighted as an important factor influencing breast 
cancer survivors adherence to and persistence with their medication (Peddie, 2021). 
 
 

 
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2.2 
RATIONALE  
The rationale for conducting this transversal real world observational study is the following: 
 There is a lack of data regarding dermatological events impact on quality of life in early breast 
cancer females receiving adjuvant endocrine therapy: dermatological toxicities induced by 
adjuvant endocrine therapy 
rarely described in literature). This transversal real word observational study aims to describe 
the dermatological toxicities reported by patients with breast cancer treated with adjuvant 
endocrine therapy.  
 The justification for the targeted population is the following: 
- 
Age and sex 
Females aged above 18 years old will be considered in this study. Breast cancer mainly concern 
females as only 1% of males are affected according to ESMO (Cardoso, 2019). Considering 
females about a quarter of breast cancers occurred before age 50, and less than 5% before age 35 
(Cardoso, 2019). The same range of proportion is therefore expected in the study to be 
representative of the general population. 
- 
Early breast cancer status 
All early breast cancer stages status according to WHO (Tan, 2020, Cardoso, 2019; Lakhani, 
2012) and TNM classification (Teichgraeber, 2021) will be included in the study in order to have 
an overall view of the whole population of patients treated with adjuvant endocrine therapy for 
breast cancer. The cancer status will be reported in the characteristics baseline. 
 Justification of the study timepoint 
To avoid catching dermatological reactions related to prior treatments, only early breast cancer 
female patients treated, with ongoing adjuvant endocrine therapy in monotherapy initiated 2 years 
(up to 1 year and 9 months) to 3 years (up to 3 years and 6 months) ago will be included.  
 Justification of the Quality of Life (QoL) questionnaires 
For the primary objective, the Dermatology Life Quality Index (DLQI) questionnaire will be used 
for evaluating the overall quality of life regarding dermatological concerns.  
 
 

 
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For the secondary objectives, the QoL questionnaires were selected according to the common 
adverse events related to dermatological toxicities: 
 Skindex-16 questionnaire for dermatological disease on quality of life (Chren, 2012), 
 Hairdex questionnaire for evaluating of disease-specific quality of life in patients with hair 
diseases (Fischer, 2001), 
 ItchyQoL questionnaire for assessing quality of life in patients with chronic pruritus (Gabes, 
2021). 
 
 

 
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3 
STUDY OBJECTIVES 
3.1 
PRIMARY OBJECTIVE 
To measure the quality of life related to dermatological toxicities, using DLQI questionnaire, in 
female patients with early breast cancer (defined according to WHO classification and the 8th edition 
of the TNM staging system), being treated with ongoing adjuvant endocrine therapy in 
monotherapy, initiated 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 6 months) 
before inclusion in the study. 
3.2 
SECONDARY OBJECTIVES 
Secondary objectives aim, in female patients with EBC, being treated with ongoing adjuvant 
endocrine monotherapy initiated 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 
6 months) before inclusion in the study, to describe: 
1. The dermatological quality, using Skindex-16, Hairdex, and ItchyQoL  
2. The real-world dermatological toxicities present at inclusion. 
3. The demographics characteristics, and the clinical characteristics. 
3.3 
EXPLORATORY OBJECTIVES  
To describe real-world dermatological toxicities, from the beginning of their endocrine therapy to 
the time of data collection, of female patients with EBC, being treated with ongoing adjuvant 
endocrine monotherapy initiated 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 
6 months), before inclusion in the study. 
 
 
 

 
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4 
RESEARCH METHODS 
4.1 
STUDY DESIGN 
This is an European (including France, Greece, Italy, Spain), multicenter (from the European 
Academy of Dermatology and Venereology - European Task Force 
), real word observational, cross-sectional study, to describe the quality of life related to 
dermatological toxicities, in female patients with EBC, treated with ongoing adjuvant endocrine 
monotherapy initiated 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 6 months) 
before inclusion in the study. 
This is a cross-sectional, non-interventional study in which physicians and patients will follow local 
clinical practice. The study will not provide or recommend any treatment or procedure. 
 
Participating sites will be encouraged to propose the study to all patients meeting the eligibility 
criteria, in a consecutive manner, when they come for consultation, in order to minimize bias in 
patient selection. Around 9 centers are expected to participate in the study. 
 
Eligible patients will be selected among patients treated with ongoing adjuvant endocrine 
monotherapy initiated 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 6 months) 
before inclusion, in one of the study centers. Patients will be asked to complete 4 questionnaires at 
the time of their inclusion. Medical history, demographics, clinical characteristics, current and 
dermatological toxicities from the beginning of their endocrine therapy to the time of data collection 
will be collected from their medical charts.  
As this is a transversal study, there will not be any follow-up, and no safety data will be collected. 
However, the investigator shall report all necessary information about any suspected adverse 
reaction to a product to the regulatory agency and to the marketing authorisation 
holder/manufacturer.  
 
The decision to prescribe adjuvant endocrine monotherapy will be taken before the inclusion in the 
study. The study will not impose any treatments or visits. 
European countries, including France, Greece, Italy, and Spain, will enroll patients. Dedicated 
reference centers (Dermatology For Cancer Patients Task Force) will be able to recruit.  
The study will address oncologists, oncodermatologists and/or radiotherapists treating patients with 
adjuvant endocrine therapy. Physicians will be selected on their clinical research experience, the 
availability of their resources to conduct the study and their ability to recruit and follow a sufficient 
number of patients in the study. Only patients who provide written informed consent or non-
opposition to data collection, as per local regulations, will be enrolled.  
The enrolment period is expected to extend up to 12 months from the study start. 

 
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Approximately 156 eligible patients will be selected. 
4.2 
POPULATIONS 
4.2.1 Study population  
Approximately 156 patients will be included in the study to get about 140 evaluable patients. 
The source population in this study is female patients suffering from EBC and treated with adjuvant 
endocrine monotherapy for 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 6 
months), who spontaneously visit a hospital from the EADV European task force, in European 
countries (including France, Greece, Italy and Spain). They will be invited to participate in the 
study, during the inclusion period. The study population is the source population meeting eligibility 
criteria listed hereafter during the inclusion period. 
4.2.1.1 Inclusion criteria 
Patients will be eligible for inclusion if they fulfill ALL The following criteria: 
1. Female a
. 
2. Histologically confirmed diagnosis of EBC, according to the WHO criteria (Lakhani, 2012; 
Cardoso, 2019; Tan, 2020) and the TNM classification, (Teichgraeber, 2021) at any time 
before inclusion. 
3. Still being treated with adjuvant endocrine monotherapy, initiated 2 years (up to 1 year and 
9 months) to 3 years (up to 3 years and 6 months) before the inclusion in the study. 
4. Signed Informed Consent Form (ICF) or non-opposition, according to local regulations. 
4.2.1.2 Exclusion criteria 
Patients will not be eligible for inclusion if they fulfill ANY of the following criteria: 
1. Patients not able to read, understand and complete Questionnaires in local language. 
2. Patients with chronic dermatological conditions (treated or not) before initiating the 
adjuvant endocrine therapy that could interfere with the quality of life. 
3. Patients with concomitant targeted therapies with adjuvant endocrine therapy such as 
CDK4/6 inhibitors or trastuzumab, and patients with ongoing treatment with neratinib.. 
4. Patients having relevant or severe comorbidities requiring complex therapeutic treatment. 
5. Patient having a persistent post-chemotherapy alopecia (at least of grade 1). 

 
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4.2.2 Patient selection  
4.2.2.1 Study centers 
The target countries for study participation will include European countries such as France, Greece, 
Italy, and Spain.  
4.2.2.2 Patient selection 
 Study initiation, patient selection, and data abstraction are planned to start in 2024. 
 All female 
with early breast cancer who are treated with any adjuvant 
endocrine monotherapy for 2 years (up to 1 year and 9 months) to 3 years (up to 3 years and 6 
months) before the inclusion date. 
 After verification of the eligibility criteria, the investigator or qualified designee will inform the 
patient about: 
- 
The study objectives, 
- 
The possibility of refusing to participate without any prejudice to the relationship with the 
, 
- 
Processing of personal data that will be collected during this study and the rights of access, 
opposition, and rectification to this data. 
The patient will be provided with a written or electronic information sheet about the study prior to 
data abstraction from patient records and completion of the questionnaires. If the patient agrees to 
participate, she will be asked to provide their written informed consent or non-opposition to study 
participation to the investigator (depending on local regulations), which will be documented in the 
 before data collection. 
 
Data that will be collected upon study inclusion are detailed below: 
 Patient demographics, 
 History of early breast cancer stage and date of diagnosis, 
 History of procedures and treatments before the initiation of the adjuvant endocrine therapy 
in monotherapy, 
 History of the adjuvant endocrine therapy in monotherapy (date of initiation, type of 
treatment), 

 
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 History of dermatological toxicities from the beginning of current treatment to the time of 
inclusion, 
 Ongoing dermatological toxicities, 
 Dermatological care and sun protective behaviors, 
 Quality of life questionnaires. 
4.3 
STUDY OUTCOMES 
The outcomes of this real word observational study are purely descriptive. They aim to describe 
mainly the quality of life related to dermatological toxicities of female patients with early breast 
cancer under adjuvant endocrine therapy in monotherapy, and also the demographics and clinical 
characteristics at the time of inclusion. 
 
 
4.3.1 Primary outcome 
The primary outcome is the description of the quality-of-life data collected at the time of inclusion 
using the validated DLQI questionnaire. The DLQI consists of 10 questions concerning patients' 
perception of the impact of skin diseases on different aspects of their health-related quality of life 
over the last week, including symptoms, feelings, daily activities, leisure, work, school, personal 
relationships, and treatment. 
 
The primary endpoint is the rate of patients with a DLQI score  6. The DLQI is calculated by 
summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher 
the score, the more quality of life is impaired:  
 0  1 corresponds to no effect at all on patient's life, 
 2  5 corresponds to small effect on patient's life, 
 6  10 corresponds to moderate effect on patient's life, 
 11  20 corresponds to very large effect on patient's life,  
 21  30 corresponds to extremely large effect on patient's life. 

 
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4.3.2 Secondary outcomes 
1. Quality of life data collected at the time of inclusion using the Skindex-16, Hairdex, and 
ItchyQoL questionnaires. 
The Skindex-16 includes items distributed across three domains symptoms (items 1 to 4), 
emotions (items 5 to 11) and functioning (items 12 to 16) and are answered on a seven-point 
Likert scale (varying from 0-never bothered, to 6-always bothered), which represents the 
frequency with which the skin problem bothered the respondent during the past week. This 
is a 0-100 scale, higher the score, the more quality of life is impaired. 
 
The Hairdex  is a valuable tool for evaluating disease-specific QoL in patients with hair 
disorders. It consists of 48 questions across five sections: symptoms, functioning, emotions, 
self-confidence, and stigmatization. Each question is self-graded on a scale of 0-4, with a 
.  
 
The ItchyQoL is a questionnaire used to measure the QoL in patients with chronic pruritus. 
It is composed of 22 items regarding symptoms, functions, emotions and self-perception, 
and is currently under copyright protection. In addition to the total score, a subscore for 
"symptoms", "functioning" and "emotions" can also be calculated. Each item is rated on a 
5-point scale, ranging from 1 = never to 5 = all the time. 
2. Ongoing dermatological toxicities reported by investigator according to Common 
Terminology Criteria for Adverse Events (CTCAE) (version 5.0, November 2017): 
a. Type of toxicity 
b. Surface area involved (except for nails and oral dryness) 
c. Start date 
d. Clinical grading of the toxicity 
3. Demographics, and clinical characteristics at the time of inclusion, including the following 
items: 
a. Age, gender, weight, height 
b. Menopausal status 
c. Date of cancer diagnosis 
d. Primary tumor location 
e. T stage 
f. Prior therapies for breast cancer (type, agent name, start date, stop date) 

 
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g. Endocrine therapy (agent name, start date) for breast cancer 
h. Current dermatological care and sun-protective behaviors  
4.3.3 Exploratory outcomes 
History of dermatological toxicities from the beginning of current treatment to the time of inclusion, 
including: 
a. Type of dermatological toxicity  
b.  Surface area (except for nails and oral dryness) 
c. Start date and end date 
d. Grade of the toxicity, if available 
e. Change in hormonal treatment (adaptation, interruption), if applicable 
4.3.4 Subgroups of interest  
The following subgroups described are of interest: 
 Age repartition by class (< 35 years old, 35-50, 50-65, > 65 years old) 
 Menopause status 
 Therapeutical choice before the 2/3 years of adjuvant endocrine therapy (2 years up to 1 year 
and 9 months, to 3 years up to 3 years and 6 months). 
- 
Radiotherapy (yes / no) 
- 
Chemotherapy (yes / no), if yes, the information whether taxane was received or not will be 
collected 
- 
Adjuvant (yes/no) 
- 
Neoadjuvant (yes/no) 
- 
Target therapy (yes / no) 
- 
Type of adjuvant endocrine therapy 
 
Analyses of primary, secondary, and exploratory outcomes may be performed for some or all of 
these subgroups, subject to pertinence and the number of patients in each subgroup. 

 
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4.4 
DATA SOURCES 
Data for each patient will be collected until the date of inclusion. Questionnaires will be filled by 
patients at the time of their inclusion and data will be collected in their medical records during data 
abstraction period. 
The source of collected data will include all elements that constitute a reliable source of patient-
level information and are available at the center.  
This includes inpatient medical charts (e.g., consultation notes, discharge summaries, laboratory 
test results, recorded prescription data and any other documentation of communication with other 
health care providers). The center investigator will be responsible for ensuring that all the required 
data is collected and entered into an electronic Case Report Form (eCRF). The pseudonymization 
of entered data will be guaranteed by the use of a Subject Identifier. This pseudonymization will be 
maintained in the database used for statistical analysis.  
 
Electronic Patient Reported Outcome (ePRO) will be used to collect questionnaires. Patients will 
be asked to fill questionnaires on site using tablets specifically dedicated to the present study. 
 
Key data items that will be collected are listed in section Study outcomes. 
4.5 
STUDY SIZE 
Within this study, it is planned to recruit 156 patients. 
Accrual of 140 evaluable patients permits to estimate a 95% confidence interval of a proportion 
equals to 40% with an accuracy of +/-8%. The following table presents the accuracy for different 
proportions:  
 
 
Proportion of DLQI score 
6 
 
10% 
20% 
30% 
40% 
Accuracy (%) 
+/-5 
+/-6.5 
+/-7.5 
+/-8 
 
Assuming a rate of around 10% of non-evaluable patients (missing data), 156 patients will be 
included to reach 140 evaluable patients. 
4.6 
DATA MANAGEMENT 
A Data Management Plan will be created before the start of data collection and will describe all 
functions, processes, and specifications for data collection, cleaning and validation to ensure that 
the data are as clean and accurate as possible when presented for analysis. Data collection and 
validation procedures will be detailed in the appropriate operational documents. 
 

 
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A study monitoring plan, including for-cause monitoring, that is appropriate for the study design 
will be developed and implemented. Data quality control (QC) will be performed remotely and at 
the center level, where permissible according to local regulations, by qualified designated personnel 
under professional secrecy. 
 
All medical data will be confidential. Pierre Fabre Médicament, as the Sponsor of the study and 
data controller, is responsible for the processing of personal data in accordance with the 
provisions of Regulation 2016/679/EU of the European Parliament and of the Council of 27 April 
2016 on the protection of natural persons with regard to the processing of personal data and the 
free movement of such data (GDPR), the data collected being for research purposes in the field of 
health, the legal basis of the processing being the legitimate interest of the data controller. 
 
Data from patient medical records will be entered by the investigator or delegated data entry 
specialists in the eCRF. The qualified designee for data entry must ensure that: 
 Data entry is performed in a timely manner, 
 Data entry is complete and accurate, 
 All eCRF data are verifiable in the source documentation, 
 Data queries are resolved and documented by authorized study staff, 
 All eCRFs are approved with an electronic signature (changes to data previously submitted will 
require a new electronic signature to acknowledge/approve the changes). 
 
All data collected within the eCRF will be approved and electronically signed and dated by the 
investigator. This approval will acknowledge the i
as being complete and accurate.  
 
At study end and before the final statistical analysis, the eCRF and other study data will be locked 
to further additions or corrections. Locking the study data represents the acknowledgement that all 
data have been captured and confirmed as accurate. 
Quality assurance department representatives from Pierre Fabre Médicament and/or Contract 
Research Organization (CRO) may visit a study center to conduct quality assurance audit and ensure 
the study is conducted in compliance with protocol, Standard Operating Procedures and all 
applicable legal requirements. 
 
 

 
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4.7 
DATA ANALYSIS 
4.7.1 General considerations 
Statistical analyses will be fully described in a Statistical Analysis Plan (SAP). Analyses will be 
conducted with SAS® software, version 9.4 or higher.  
Analyses will be descriptive in nature, as no hypothesis will be tested. 
Demographic and clinical characteristics will be presented in the overall population using usual 
statistics. Quantitative data will be summarized as median, min, max and number of missing data. 
Qualitative variables will be described as number, percentage and number of missing data. 
4.7.2 Data-set definition 
Analysis population (full analysis set) consists of all patients fulfilling inclusion and exclusion 
criteria with at least one QoL score not missing. 
4.7.3 Analysis of primary outcomes  
and percentage with corresponding 95% interval (binomial exact). 
4.7.4 Analysis of secondary outcomes 
Quality of Life Scores will be calculated using recommendations provided in the literature and will 
be described by means, standard deviations, medians, and percentages. The percentage of missing 
Quality of life scores will be also provided and p
generated to assess the impact on QoL scores.  
Dermatological toxicities ongoing at inclusion will be described. Each of the following will be 
assessed: 
 Dermatological toxicities by type, 
 Dermatological toxicities for each type and by grade. 
Frequency, percentage with 95% Confidence Interval (CI) will be computed for each event. 
 
 

 
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4.7.5 Analysis of exploratory outcomes 
History of dermatological toxicities will be described. Each of the following will be assessed: 
 Dermatological toxicity by type, 
 Dermatological toxicity for each type and by grade. 
4.7.6 Missing data 
In general, missing data will not be imputed (except for dates) and the data will be analyzed 
according to the complete case approach. Proportion of missing data will be provided for all 
variables during descriptive analyses.  
 
4.7.7 Interim analysis 
As regard to the descriptive nature of the study, an interim analysis will be performed on Q2-Q3 
2025 on the patients included in the study coordinator
 (France) until the 15th of May 2025 in 
order to communicate preliminary results 
characteristics and the quality-of-life data collected at the time of inclusion using the validated 
DLQI questionnaire (i.e. primary outcome) and the Skindex-16 (i.e. one of the secondary 
outcomes). Details of the interim analysis will be described in the SAP. 
 
4.8 
QUALITY CONTROL 
After formal agreement of participation, center
designated Clinical Research Associate. The frequency of subsequent contacts (monitoring on 
center visits, phone, or e-mail) with the centers will be decided with the Sponsor and will be adapted 
if specific difficulties are identified during the training. A study monitoring plan, including for-
cause monitoring, that is appropriate for the study design will be developed and implemented. Data 
QC will be performed remotely and at the center level, where permissible according to local 
regulations, by qualified designated personnel under professional secrecy. 
To ensure compliance with relevant regulations, data generated by this study must be available for 
inspection upon request by representatives of national authorities, and local health authorities as 
applicable, the Sponsor and representatives, and the Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) for each study center. The investigator will permit authorized representatives 
of the Sponsor, the respective national or local health authorities, and auditors to inspect facilities 
and records relevant to this study.  

 
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The Sponsor or representative CRO is responsible for verifying the eCRFs at regular intervals 
throughout the study to verify adherence to the protocol and the Sponsor or representative CRO 
applicable SOPs, completeness, accuracy and consistency of the data, and adherence to the Good 
Pharmacovigilance Practice (GVP): Module VI  Collection, management and submission of 
reports of suspected adverse reactions to medicinal products (EMA/873138/2011 Rev 2, 2017), 
International Conference of Harmonization (ICH) Good Clinical Practice (GCP) (ICHE6, 2017) 
and local regulations on the conduct of clinical research. Source data to be reviewed during this 
study will include but will not be restricted to: patient medical files, patient questionnaires and 
pathology reports. All key data must be recorded in the patient hospital notes.  
 
During and/or after completion of the study, quality assurance auditor(s) named by the Sponsor or 
the regulatory authorities may wish to perform on-center audits. The investigator will be expected 
to cooperate with any audit and provide assistance and documentation (including source data) as 
requested.  
The Sponsor representatives are responsible for contacting and visiting the investigator for the 
purpose of inspecting the facilities and, upon request, inspecting the various records of the clinical 
study (e.g., eCRFs and other pertinent data) provided that patient confidentiality is respected.  
The investigator agrees to cooperate with the monitors to ensure that any problems detected in the 
course of these monitoring visits, including delays in completing CRFs, are resolved.  
4.9 
STUDY MANAGEMENT 
PIERRE FABRE MEDICAMENT is the Sponsor of the study. The Sponsor will be responsible, 
among others, for: 
 Initiating, managing, and financing the study, 
 Selecting the qualified Principal Investigators, 
 Providing necessary information to the study centers to allow them to successfully conduct 
the study, 
 Obtaining the investigator agreement from all participating study centers, 
 Ensuring that the required regulatory approvals / favorable opinions are received, 
 Ensuring that any modifications required by the ethics committee or regulatory authority are 
implemented, 

 
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 Performing and documenting root cause analysis and implementing appropriate corrective 
and preventive actions if non-compliance significantly affects or has the potential to 
significantly affect subject protection or reliability of clinical study results, 
 Ensuring that study procedures comply with applicable regulation for data protection. 
4.10 LIMITATIONS OF THE RESEARCH METHODS 
The biggest strength of this study is that it will be able to yield data on the dermatological toxicities 
in real-life conditions of use and in the current treatment landscape, and in a varied profile of 
patients. 
 
However, an observational study comes with its limitations which are as follows: 
1. Selection bias:  
The target population (the entire set of individuals to which the findings of the study are to be 
extrapolated) of this study is the population of female patients suffering from EBC, currently 
treated with adjuvant endocrine monotherapy, initiated 2 years (up to 1 year and 9 months) to 3 
years (up to 3 years and 6 months) before the inclusion in the study, in real-life setting Sample 
representativeness may be compromised by selection biases. The sites who will accept in 
participating in the study could preferentially be those who are more involved in assessing 
quality of life of their patients. They can preferentially be those who have a more significant 
number of patients corresponding to the target population in their practice. To prevent patient 
selection bias, participating investigators will be advised to recruit consecutively eligible 
patients who meet the inclusion criteria. 
Patients (or their next of kin/legal representative) who refuse to participate may limit the 
representativeness of the study results. Confounding can occur due to unobservable 
characteristics of patients. Investigators will be asked to prospectively enrol consecutive 
patients who meet the eligibility criteria. 
2. Design:  
Since some data in the study will be extracted from past medical records, investigators will have 
no control over how the data was recorded and managed prior to the study. 
3. Missing data:  
Depending on physician practices, some data might not be systematically measured or available. 
COVID-19 pandemic could also contribute to missing data. Missing data can bias the 
descriptions if it is not completely random. Even in cases where missing data is truly random, a 
potential impact on the precision of the estimates cannot be overlooked. Remote Monitoring 
procedures will be implemented, wherein it will be ensured that the eCRFs have been 

 
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comprehensively filled. Sensitivity analyses may be carried out, where applicable, to estimate 
if a non-negligible proportion 
of missing data is observed for a certain parameter, groups of patients with and without missing 
data may be compared.  
PROs will be collected with tablets, which minimizes the number of missing data through the 
use of drop-down lists and mandatory fields.  
4. Memory bias:  
As dermatological events will be collected during the last 2 years (up to 1 year and 9 months) 
to 3 years (up to 3 years and 6 months), they could be underestimated reported number of 
punctual or mild dermatological toxicities.  
 
5. Heterogeneity between study centers:  
Since this is an observational study of real-life dermatological toxicities, reporting of toxicities 
can vary widely based on standard practices in each country and/or investigating center. This 
could lead to an over or under-reporting of certain data. Where deemed appropriate subgroup 
analyses by country could be performed for certain outcomes or variables of interest.  
6. Measurements bias: 
Data regarding primary and secondary outcomes are mainly declarative data collected directly 
from patient and may thus not completely reflect reality. Data collected through self-
questionnaire which are completed by the patient may lead to a reporting bias. However, as this 
is data related to quality of life and facts experienced by patients, this collection method was the 
best compromise. To maintain confidentiality and to avoid bias, data gathered at the patient level 
will not be accessible to investigators and only be processed in the research perspective of this 
study. 
Further details on how biases in the study design are to be addressed will be elaborated in the SAP. 
 
 

 
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5 
PROTECTION OF HUMAN SUBJECTS AND LOCAL REGULATORY ASPECTS 
The study will be conducted in accordance with the ethical principles of the declaration of Helsinki 
and the General Data Protection Regulation (UE 2016/679) and other local regulatory requirements.  
The need to submit the protocol to an Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) and the requirement of informed consent will be considered in accordance with local 
law. Any amendments to the study protocol, as well as the associated Informed Consent Form will 
be submitted to the appropriate IRB/IEC for approval prior to implementation, according to the 
requirement of each IRB/IEC. 
 
This observational study does not involve any changes in the local care standards of the patients 
participating in the study, does not compromise their physical or psychological integrity and does 
not require any special follow-up visits for these patients. 
 Each patient will be fully informed before enrollment in the study and start of data abstraction, and 
their written consent or verbal non-opposition will be taken, as per the local regulations of each 
target country.  
Wherever applicable, an Informed Consent Form waiver will be obtained, depending on approval 
by Ethics Committees and/or local regulations.  
 
Investigators shall ensure that personal identifiers will be removed from any study files that are 
accessible to non-study personnel in accordance with applicable laws and regulations. In case of 
sub-contracting, it is the responsibility of the service provider concerned to ensure that 
computerized processing is in conformity with the applicable national regulations regarding the 
protection of personal data and, if necessary, carry out any formality with the supervisory authorities 
and transmit the declaration date to Sponsor. 
 
The investigator must ensure that patient confidentiality is maintained. It is required that the 
investigator and institution permit authorized representatives of the Sponsor, of the regulatory 
medical records for verification of study-related procedures and data. Direct access includes 
examining, analyzing, verifying, and reproducing any records and reports that are important to the 
evaluation of the study. A
and responsibility of the principal investigator or their center personnel. The investigator is 
obligated to inform and obtain the consent of the patient to permit named representatives to have 
access to their study-related records without violating the confidentiality of the patient. The study 
will be registered on ClinicalTrials.gov and will be in national registries where applicable. 
 
 

 
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6 
MANAGEMENT 
AND 
REPORTING 
OF 
ADVERSE 
EVENTS/ADVERSE 
REACTIONS 
As the objective of this study is not to assess the efficacy nor the safety of a Pierre Fabre 
Médicament product and as no solicited data of safety or Pierre Fabre Médicament product are 
collected, the investigator shall report all necessary information, about any suspected adverse 
reaction to a product, to the regulatory agency or to the marketing authorization 
holder/manufacturer of the concerned product, according to the local regulation. 
 
 

 
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7 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS  
Data will be analyzed and presented in a final report which will be submitted to the Sponsor. This 
final report will help in the preparation of one or more publications. 
 
Of note, no interim clinical study report will be provided. 
 
Any written or oral communication of the research results will receive prior consent of the Sponsor 
and, if necessary, of any committee formed for the research. All publications will follow the 
International Committee of Medical Journal Editors guidelines (International Committee of 
Medical Journal Editors, 2023). In addition, communication in appropriate scientific meetings 
will be considered.  
 
 

 
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8 
OWNERSHIP OF RESULTS 
The results of the Study shall be owned exclusively by PIERRE FABRE MEDICAMENT and/or 
any designee shall have free use of the same in France and worldwide. 
Such ownership shall apply to any data, patentable or non-patentable inventions, know-how and 
any invention resulting from the Study. 
 
 

 
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9 
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Lubián, 2022 
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Madigan, 2020 
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Tan, 2020 
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Wagner, L.I., and Lacouture, M.E. (2007). Dermatologic toxicities associated with EGFR 
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36. 
 

 
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10 APPENDICES 
10.1 Signature Pages 
AGREEMENT PAGE  
 
Protocol Version 3.0 dated 23 May 2025 
  
 
Sponsor Medically Qualified Representative Signatory:  
 
 Global Medical Advisor 
 
 
 
 
 
 
 
   
  Date  
 
  Real-word Evidence Project Leader 
 
 
 
 
 
 
 
   
  Date  
 
 
 
  
 
 
 

 
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Coordinating Investigator Signatory:  
  
-  Oncodermatologist  - Chair of the European Task Force 
 
 
 
 
 
 
  
  
  
  Date  
 
 
Statistician:  
 
Head Biostatistics & Health Data Science Unit / Methodologist Biostatistician
 
 
 
 
 
 
 
  
  
  
  Date  
 
  
Statistician Real-world Evidence:  
 on behalf of 
  
 
 
 
 
 
 
  
  
  
  Date  
 
 
 
 

 
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Other signatures 
 
 
Principal Investigator signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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10.2 Questionnaires 
10.2.1 DLQI questionnaire - 2019 
 

 
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10.2.2 Skindex-16 questionnaire  2001  
Skindex16 © The Regents of the University of California, 2001 
 
 
 
 

 
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10.2.3 Hairdex questionnaire  version 2010 
Hairdex: Fischer, 2001 
 

 
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10.2.4 ItchyQoL questionnaire  Version 2012 
 
 

 
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