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Future Oncology

ISSN: (Print) (Online) Journal homepage: www.tandfonline.com/journals/ifon20

Abemaciclib for treating patients with HR+/HER2-

metastatic breast cancer: a real-world study in

France, Italy and Spain

Isabel Blancas, Jessica Grosjean, Rebecca Pedersini, Carlotta Buzzoni,

Ghassan Sleilaty, Alberto Molero, Antonella Tamma, Nadia Chouaki, Manuel

Atienza, Anna Emde, Sara Siddi, Rodrigo Sanchez Bayona, Lucia Del Mastro

& Walid Fakhouri

To cite this article: Isabel Blancas, Jessica Grosjean, Rebecca Pedersini, Carlotta Buzzoni,

Ghassan Sleilaty, Alberto Molero, Antonella Tamma, Nadia Chouaki, Manuel Atienza, Anna

Emde, Sara Siddi, Rodrigo Sanchez Bayona, Lucia Del Mastro & Walid Fakhouri (08 Aug 2024):

Abemaciclib for treating patients with HR+/HER2- metastatic breast cancer: a real-world study

in France, Italy and Spain, Future Oncology, DOI: 10.1080/14796694.2024.2368455

To link to this article: https://doi.org/10.1080/14796694.2024.2368455

© 2024 The Author(s). Published by Informa

UK Limited, trading as Taylor & Francis

Group

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FUTURE ONCOLOGY

https://doi.org/10.1080/14796694.2024.2368455

RAPID COMMUNICATION

Abemaciclib for treating patients with HR+/HER2- metastatic breast cancer: a

real-world study in France, Italy and Spain

Isabel Blancas*,a,b,c , Jessica Grosjeand, Rebecca Pedersinie, Carlotta Buzzonif

, Ghassan Sleilatyf

, Alberto

Molerof

, Antonella Tammaf

, Nadia Chouakif

, Manuel Atienzaf

, Anna Emdef

, Sara Siddig,h, Rodrigo Sanchez

Bayonai

, Lucia Del Mastroj,k and Walid Fakhourif

aHospital Universitario Clínico San Cecilio, 18016 Granada, Spain; bMedicine Department, Granada University,

18010, Granada, Spain; c

Instituto de Investigación Biosanitaria de Granada (ibs Granada), 18012, Spain; dCentre de

Cancérologie Les Dentellières, 59300, Valenciennes, France; eBreast Unit – Oncologia, ASST Spedali Civili di Brescia,

25213, Brescia, Italy; f

Eli Lilly & Company, 46285, Indianapolis, Indiana, USA; gInstitut de Recerca Sant Joan de Déu (IRSJD),

Esplugues de Llobregat, 08950, Barcelona, Spain; hCentro de Investigación Biomédica en Red de Salud Mental, 28029, Madrid,

Spain; i

Unidad de Cáncer de Mama y Ginecológico, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain; j

Unità Operativa

Complessa, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132, Genova, Italy; k

Dipartimento di

Medicina Interna e Specialità Mediche, Università di Genova, 16132, Genova, Italy

ARTICLE HISTORY

Received 22 November 2023

Accepted 12 June 2024

KEYWORDS

abemaciclib; HR+/HER2-

advanced/metastatic

breast cancer; real-world;

treatment outcomes;

treatment patterns

ABSTRACT

Aim: This real-world study aimed to describe patient and clinical characteristics, treatment patterns

and outcomesfor patients withHR+/HER2- metastatic breast cancerreceiving abemaciclib in France,

Italy and Spain. Materials & methods: A multicenter chart review was conducted for adult females

with HR+/HER2- advanced/metastatic breast cancer who received abemaciclib in routine care. Realworld progression-free survival (rwPFS) was estimated via Kaplan-Meier curves. Results: This study

included 151, 173 and 175 patients from France, Italy and Spain, respectively. Abemaciclib was

mostly prescribed as first-line therapy concomitantly with hormone therapy. Median rwPFS was

>20 months and the 1-year rwPFS rate was >70%. Conclusion: Effectiveness was similar across the

three countries and aligns with pivotal studies.

Plain language summary: Abemaciclib use in the clinic in France, Italy & Spain

This study describes patients, the treatments they have received and the results of those treatments

for patients with the most common type of advanced breast cancer. These patients were taking

abemaciclib plus hormonal therapy in routine breast cancer care in France, Italy and Spain. The

information used to conduct this study was taken from patients’ medical charts. In this real-world

study, abemaciclib was mostly used asthe initial treatment for advanced breast cancer. Abemaciclib

effectiveness was similar across the three countries confirming findings from previous studies. Our

study supports the use of abemaciclib for patients with HR+/HER2- advanced breast cancer.

1. Background

Breast cancer is the most commonly diagnosed type of

cancer, accounting for one in six cancer deaths in women

worldwide [1]. Despite recent advancesin early detection

and treatment, breast cancer prevalence is predicted to

continue to increase throughout 2020–2040 [2]. In France,

Italy and Spain, breast cancer is one of the most diagnosed types of cancer and accounts for 7.6, 7.2 and 5.8%

of cancer-related deaths,respectively [3–5]. Itis estimated

that by 2040, over 3 million new cancer cases and over

1 million deaths per year will be caused by breast cancer [2]. Approximately 20–30% of early breast cancers will

progress into metastatic breast cancer [6]. Median overall survival for patients with metastatic breast cancer is

only 2–3 years, although the range is wide [7] reflecting

the variability in tumor biology [8]. Indeed, it is known

that triple negative breast cancer is associated with the

worst overall survival while HR+/HER2-, the most common breast cancer subtype, is associated with a better prognosis. To date, prolonged survival has been the

best treatment outcome for advanced breast cancer [9–

11]. More specifically, recent advances in clinical research

demonstrated survival gains for HR+/HER2- metastatic

breast cancer due to novel treatments in the landscape.

CONTACT Isabel Blancas iblancas@ugr.es

Supplemental data for this article can be accessed at https://doi.org/10.1080/14796694.2024.2368455

© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License

(http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly

cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the

author(s) or with their consent.

2 I. BLANCAS ET AL.

CDK4/6 inhibitors are cell cycle inhibitors that have

become a standard of care in the treatment of advanced

breast cancer [12]. Abemaciclib, an oral selective small

molecule inhibiting CDK 4/6, has shown efficacy in randomized controlled trials (RCTs) for the treatment of

breast cancer [13–15]. In the European Union (EU), abemaciclib was approved in 2018 and is indicated for the

treatment of HR+/HER2- locally advanced or metastatic

breast cancer in combination with an aromatase inhibitor

(AI) or fulvestrant asinitial endocrine-based therapy, or in

women who have received prior endocrine therapy. Abemaciclib was fully available in France, Italy and Spain by

February 2019, December 2019 and May 2019, respectively. Abemaciclib has shown efficacy in clinical trials for

the treatment of metastatic breast cancer both as a single agent and in combination with hormone therapy [13–

16]. Clinical benefits of abemaciclib in combination with

hormone therapy have been demonstrated for patients

who initiated abemaciclib as first-line treatment and for

patients who were heavily pre-treated [14,15]. Current

real-world data on demographics, clinical characteristics,

treatment patterns and treatment outcomes for patients

treated with abemaciclib have mostly been studied in

populations from the United States (US) and Japan [17–

20]. Additional data from a Named Patient Use (NPU) programme of abemaciclib in Spain from the retrospective

AbemusS study have been previously published [21]. Following the approval of abemaciclib in the EU, real-world

data on patients treated with abemaciclib in the EU are

needed in order to inform treatment decisions.

This study aimed to retrospectively assess patient and

clinical characteristics, treatment patterns and outcomes

for patients with HR+/HER2- advanced/metastatic breast

cancer treated with abemaciclib in a European population. Data from routine clinical practice in three European

countries, namely France, Italy and Spain, are presented.

Additionally, relevant similarities and differences among

the three countries are explored.

2. Methods

2.1. Study participants & data collection methods

This study is a retrospective observational study based

on a multicenter clinical chart review in France, Italy and

Spain (Supplementary Table S1). Adult females with a

HR+/HER2- advanced/metastatic breast cancer diagnosis

(stage IIIb, IIIc or IV), as defined by the American Society

of Clinical Oncology (ASCO)/College of American Pathologists(CAP) guidelines[22,23], who received abemaciclib

in their initial treatment regimen were included. A followup of at least 3 months post-abemaciclib initiation was

required. Patients who participated in a clinical trial at any

time after abemaciclib initiation were excluded.

In France, clinical chart review was conducted over 11

sites for patients who initiated treatment with abemaciclib in the study period of February 2019 to November

2021. In Italy, clinical chart review was conducted over

eight sites for patients who initiated treatment with abemaciclib in the study period of May 2019 to March 2022. In

Spain, clinical chart review was conducted over nine sites

for patients who initiated treatment with abemaciclib in

the study period of August 2018 to January 2022.

For France, the verbal or written non-opposition to use

their data aligning with observationalstudy requirements

in France was obtained from all included patients (Number of declaration: Référence CNIL: 2219942 v 0, study

name: Étude observationnelle de patientes atteintes

d’un cancer du sein HR+/HER2- avancé/mestastatique

(aBC/mBC) et traitées par Abemaciclib.Examen des

dossiers médicaux). Ethical approval has been obtained

in Spain from the CEIM/CEI Provincial de Granada/Junta

de Andalucía: 11/01/2021 and from Ethic Committees of

each clinical satellite site; and in Italy from CER Liguria:

340/2021 - DB id 11165 and from Ethic Committees of

each clinical satellite sites. In the case of Italy and Spain,

written informed consent was obtained for all patients or

the exemption from patient consent when allowed.

Institutional review boards in Italy consisted of Comitato Etico Interaziendale A.O.U “Maggiore della Carità” Novara (CE 264/21), Comitato Etico Regionale per

la Sperimentazione Clinica della Regione Toscana/Area

Vasta Centro (20671_OSS), Comitato Etico di Brescia-ASST

Spedali Civili (NP 5056), Comitato Indipendente di Etica

Medica-ASL Brindisi (CE 224/21_Prot. 100232), Comitato

Etico Regionale Liguria (340/2021-DB id 11165), Comitato Etico per la Sperimentazione Clinica delle Provincie

di Treviso e Belluno (1118/CE Marca Trevigiana), Comitato Etico IRCCS Pascale (Prot. 50/21 OSS) and Comitato

Etico Policnico Gemelli (Prot. ID 4566). In Italy, informed

consent was obtained for all patients, except for those

exempted due to the death of participants or if patient

is not reachable. In France, the institutional review board

consisted of Commission nationale de l’informatique et

des libertés (2219942 v 0) where the (verbal / non-verbal)

non-opposition of the patients included in the study

to the use of their data was obtained. The exemption

from patient consent when allowed, as the death of participants. In Spain, institutional review boards consisted

of CEIM/CEI Provincial de Granada/Junta de Andalucía

(11/01/2021), CEIm de Albacete (2021-07 (EPA-OD)), Hospital Universitario Ramón y Cajal (03/08/2021), Comité

de Ética de la Investigación con medicamentos Hospital

12 de Octubre (21/096), Comité de Ética de la Investigación con medicamentos Consorci Hospitalari Provincial

de Castelló (28/07/2021) and Comité de Ética de la Investigación con medicamentos Fundació Sant Joan de Déu

FUTURE ONCOLOGY 3

Table 1. Patient characteristics.

Patient characteristics France Italy Spain

Number of patients, n 151 173 175

Age (years) 62.9 ± 12.7 64.1 ± 12.2 59.1 ± 12.1

Weight (kg) 67.4 ± 15.9 65.9 ± 12.3 66.5 ± 13.2

Height (cm) 161.7 ± 6.4 160.6 ± 6.5 159.1 ± 7.0

BMI (kg/m2) 25.7 ± 5.6 25.6 ± 4.8 26.3 ± 5.2

Data are presented as mean ± standard deviation unless otherwise specified. Reported age is specific to abemaciclib start. Reported weight, height and BMI

are specific to the date of last information in the clinical chart.

BMI: Body mass index.

(EOM-01-21 14/01/2021). In Spain, Informed consent was

obtained from all patientsto whom the waiver conditions

did not apply. The exemption conditions included death

of a participant and the person in charge of data entry is

external to the research team.

2.2. Information collected from medical charts

Data including demographics, clinical characteristics,

treatment patterns and treatment outcomes were

extracted from clinical charts. The following variables

were collected: age, weight (kg), height (cm), Body Mass

Index (BMI, kg/m2), Eastern Cooperative Oncology Group

(ECOG) performance status score, disease measurability,

staging, histological type, menopausalstatus, Ki-67 index

status (as determined by the patients’ treating physician

using their own clinical judgement), ER status, PgR status, treatments prior to advanced setting, perioperative

treatments, treatment lines, combination therapies and

real-world best treatment response, as assessed by the

physician or the Response Evaluation Criteria in Solid

tumors (RECIST) criteria. Additionally, data specific to

healthcare resource utilization were collected. This study

was compliant with the relevant laws and regulations

and was approved by the appropriate ethics committees.

2.3. Statistical analysis

The chart reviews in France, Italy and Spain were conducted as stand-alone and no pooled analyses of data

were planned. Variables were summarized by descriptive

statistics unless otherwise specified. Categorical variables

were reported as frequencies and proportions. Continuous variables were reported as mean ± standard deviation (SD) unless otherwise specified. Real-world Progression Free Survival (rwPFS) was defined asthe time elapsed

from the abemaciclib start date to the date of objective tumor progression or death, whichever occurred first,

reported in months (number of days/30.5). Patients who

did not have disease progression or death reported were

censored at the date of last follow-up or date of abemaciclib discontinuation. RwPFS analyses per treatment

line excluded patients who received abemaciclib in >1

therapy line. RwPFS was estimated by Kaplan-Meier (KM)

curves. For the discontinuation analysis, patients who

were still on the treatment were censored at the last date

of follow-up. Time to discontinuation was estimated by

KM curves. The Hall-Wellner approach was used to estimate the 95% confidence bands. All analyses were conducted via SAS (version 9.4 Copyright © 2017, SAS Institute Inc, NC, USA)

3. Results

3.1. Patient characteristics

In this retrospective study, 151 patients from France, 173

patients from Italy and 175 patients from Spain were

included (Table 1). Patient characteristics were similar

across the three countries. Mean age ( ± SD) at abemaciclib initiation was 62.9 ± 12.7, 64.1 ± 12.2 and

59.1 ± 12.1 yearsfor patientsfrom France, Italy and Spain,

respectively. Mean BMI ( ± SD) was also similar: 25.7 ± 5.6,

25.6 ± 4.8 and 26.3 ± 5.2 kg/m2 for patients from France,

Italy and Spain, respectively.

3.2. Clinical characteristics

At baseline, clinical characteristics were fairly similar for

patients across the three countries (Figure 1). At the

start of abemaciclib treatment, ECOG score was 0 (44.3,

77.5 and 47.3%), 1 (46.8, 18.6 and 45.3%) and 2 (8.9,

3.9 and 7.3%) for patients from France, Italy and Spain,

respectively, with Italian patients having relatively better ECOG scores (Figure 1A). Across the three countries, the majority of patients had a measurable tumor

(Figure 1B). Stage IV wasthe predominant disease stage at

first diagnosis acrossthe three countries, comprising 49.1,

34.0 and 33.8% of patients from France, Italy and Spain,

respectively (Figure 1C). Breast cancer histological type at

first diagnosis was mostly nonspecific invasive carcinoma

across the three countries (Figure 1D). Included patients

from France, Italy and Spain were predominantly postmenopausal at advanced breast cancer diagnosis, representing 71.1, 70.0 and 54.0% of patients, respectively,

although the proportion was relatively lower in Spain

(Figure 1E). Metastatic disease was identified via biopsies

at any stage of treatment for 113 (75.8%), 149 (87.1%) and

4 I. BLANCAS ET AL.

0 (n = 35, 44.3%)

1 (n = 37, 46.8%)

2 (n = 7, 8.9%)

Total = 79

France

Abemaciclib starting dose PgR Status ER Status Ki67 Status Menopausal Status Disease Histological type Disease Staging Disease Measurability ECOG

Italy Spain

Measurable (n = 81, 54.7%)

Not measurable (n = 67, 45.3%)

Total = 148

Stage 0 (n = 1, 0.9%)

Stage I (n = 15, 14.2%)

Stage II (n = 25, 23.6%)

Stage Illa (n = 8, 7.5%)

Stage IIIb (n = 3, 2.8%)

Stage IIIc (n = 2, 1.9%)

Stage IV (n = 52, 49.1%)

Total = 106

Pre-menopausal (n = 15, 13.2%)

Peri-menopausal (n = 5, 4.4%)

Post-menopausal (n = 81, 71.1%)

Post-menopausal-induced

(n = 13, 11.4%)

Total = 114

High (n = 30, 29.4%)

Low (n = 32, 31.4%)

Not tested (n = 40, 39.2%)

Total = 102

High (n = 76, 51.7%)

Low (n = 65, 44.2%)

Not tested (n = 6, 4.1%)

Total = 147

High (n = 36, 31.6%)

Low (n = 59, 51.8%)

Not tested (n = 19, 16.7%)

Total = 114

Positive (n = 110, 98.2%)

Negative (n = 1, 0.9%)

Not tested (n = 1, 0.9%)

Total = 112

Positive (n = 147, 99.3%)

Not tested (n = 1, 0.7%)

Total = 148

Positive (n = 115, 96.6%)

Negative (n = 1, 0.8%)

Not tested (n = 3, 2.5%)

Total = 119

Positive (n = 75, 70.1%)

Negative (n = 30, 28.0%)

Not tested (n = 2, 1.9%)

Total = 107

Positive (n = 126, 85.1%)

Negative (n = 18, 12.2%)

Not tested (n = 4, 2.7%)

Total = 148

Positive (n = 84, 71.2%)

Negative (n = 30, 25.4%)

Not tested (n = 4, 3.4%)

Total = 114

150 mg (n = 126, 85.7%)

100 mg (n = 16, 10.9%)

Other (n = 5, 3.4%)

Total = 147

150 mg (n = 153, 88.4%)

100 mg (n = 20, 11.6%)

Total = 173

150 mg (n = 148, 86.0%)

100 mg (n = 11, 6.4%)

Other (n = 13, 7.6%)

Total = 172

Pre-menopausal (n = 12, 7.8%)

Peri-menopausal (n = 3, 2.0%)

Post-menopausal (n = 107, 70.0%)

Post-menopausal - induced

(n = 31, 20.3%)

Total = 153

Pre-menopausal (n = 44, 27.0%)

Peri-menopausal (n = 14, 8.6%)

Post-menopausal (n = 88, 54.0%)

Post-menopausal - induced

(n = 17, 10.4%)

Total = 163

DCIS (n = 6, 4.3%)

Non-Specific Invasive Carcinoma

Type: Tubular Carcinoma

of the Breast (n = 85, 61.6%)

Non-Specific Invasive Carcinoma

Type: Mucinous Carcinoma

of the Breast (n = 2, 1.4%)

Non-Specific Invasive Carcinoma.

Type: Papillary Carcinoma of

the Breast (n = 1, 0.7%)

ILC (n = 17, 12.3%)

Other (n = 27, 19.6%)

Total = 138

DCIS (n = 5, 3.1%)

Non-Specific Invasive Carcinoma

Type: Tubular Carcinoma

of the Breast (n = 38, 23.5%)

Non-Specific Invasive Carcinoma

Type: Papillary Carcinoma pe

of the Breast (n = 1, 0.6%)

ILC (n = 19, 11.7%)

LCIS (n = 1, 0.6%)

Other (n = 98, 60.5%)

Total = 162

DCIS (n = 6, 4.7%)

Non-Specific Invasive Carcinoma

Type: Tubular Carcinoma

of the Breast (n = 91, 71.1%)

Non-Specific Invasive Carcinoma

Type: Mucinous Carcinoma

of the Breast (n = 4, 3.1%)

Non-Specific Invasive Carcinoma

Type: Cribriform Carcinoma

of the Breast (n = 1, 0.8%)

ILC (n = 24, 18.8%)

LCIS (n = 2, 1.6%)

Total = 128

Stage I (n = 25, 17.7%)

Stage II (n = 32, 22.7%)

Stage lIla (n = 15, 10.6%)

Stage IIIb (n = 6, 4.3%)

Stage IIIc (n = 15, 10.6%)

Stage IV (n = 48, 34.0%)

Total = 141

Stage I (n = 16, 11.8%)

Stage II (n = 43, 31.6%)

Stage Illa (n = 19, 14.0%)

Stage IIIb (n = 6, 4.4%)

Stage IIIc (n = 6, 4.4%)

Stage IV (n = 46, 33.8%

Total = 136

Measurable (n = 104, 66.2%)

Not measurable (n = 53, 33.8%)

Total = 157

Measurable (n = 98, 56.3%)

Not measurable (n = 76, 43.7%)

Total = 174

0 (n = 79, 77.5%)

1 (n = 19, 18.6%)

2 (n = 4, 3.9%)

Total = 102

0 (n = 71, 47.3%)

1 (n = 68, 45.3%)

2 (n = 11, 7.3%)

Total = 150

A

B

C

D

E

F

G

H

I

Figure 1. Patient clinical characteristics and abemaciclib starting dose. ECOG (A), disease measurability (B), disease staging (C), disease

histological type (D), menopausal status (E), Ki-67 index status (F), ER status (G), PgR status (H) and abemaciclib starting dose (I) for

patients initiating abemaciclib.

Reported ECOG and disease measurability are specific to abemaciclib initiation. Disease staging, histological type, menopausal status,

Ki-67 index status, ER status and PgR status are specific to initial breast cancer diagnosis. Immunohistochemistry was performed for

patients who were tested for a metastasis biopsy at any stage of treatment.

DCIS: Ductal carcinoma in situ; ECOG: Eastern Cooperative Oncology Group; ILC: Invasive lobular carcinoma; LCIS: Lobular carcinoma in

situ.

Total excludes missing data.

FUTURE ONCOLOGY 5

151

0

50

100

150

200

France Number of patients

Treatment line

86

(55.5%)

1st 2nd 3rd 4th ≥5th

29

(18.7%) 16

(10.3%)

11

(7.1%)

13

(8.4%)

68

40

62

88

Patients receiving therapy line

Patients receiving abemaciclib in therapy line

173

0

50

100

150

200

Italy Number of patients

Treatment line

110

(60.8%)

1st 2nd 3rd 4th ≥5th

47

(26.0%)

14

(7.7%)

7

(3.9%)

3

(1.7%)

19 17

46

92

Patients receiving therapy line

Patients receiving abemaciclib in therapy line

175

0

50

100

150

200

Spain Number of patients

Treatment line

92

(49.5%)

1st 2nd 3rd 4th ≥5th

33

(17.7%)

27

(14.5%) 10

(5.4%)

24

(12.9%)

105

51

82

122

Patients receiving therapy line

Patients receiving abemaciclib in therapy line

A

B

C

Figure 2. Patients who received therapy line and abemaciclib in different therapy lines in France (A), Italy (B) and Spain (C). The total

number of therapy lines where abemaciclib was selected was 155 and 181 for France and Italy, accounting for four and eight patients

who selected abemaciclib in two therapy lines, respectively. The total number of therapy lines where abemaciclib was selected was 186

for Spain, accounting for seven patients who selected abemaciclib in two treatment lines and two patients who selected abemaciclib in

three therapy lines. Percentages for “patients receiving abemaciclib by therapy line”were calculated using the previously stated total

numbers.

120 (73.2%) patients from France, Italy and Spain, respectively.

Ki-67 index, as assessed by physicians as either high

or low, was reported to be high for 29.4, 51.7 and 31.6%

and low for 31.4, 44.2 and 51.8% of patients from France,

Italy and Spain, respectively (Figure 1F). ER and PgR were

predominantly positive at diagnosis (Figure 1G & H).

The number of patients who had surgery, radiotherapy, neoadjuvant therapy and adjuvant therapy prior to

advanced staging and the proportion of patients who had

perioperative chemotherapy, hormone therapy, targeted

therapy and other therapy for treatment of breast cancer

are shown in Supplementary Figure S1.

3.3. Treatment patterns

The median treatment duration was 10.5 months

(interquartile range [IQR]: 4.8–20.0) in France, 9.6 months

(IQR: 5.8–19.3) in Italy and 9.6 (IQR: 4.1–17.0) in Spain.

Abemaciclib was predominantly prescribed as first-line

therapy for the disease across the three countries, representing 55.5% (n = 86), 60.8% (n = 110) and 49.5%

(n = 92) of patients from France, Italy and Spain, respectively (Figure 2). In addition, abemaciclib was chosen

in second (18.7, 26.0 and 17.7%), third (10.3, 7.7 and

14.5%), fourth (7.1, 3.9 and 5.4%) and fifth or more (8.4,

6 I. BLANCAS ET AL.

0

20

60

80

100

France Number of patients

Treatment line

Total 1st 2nd 3rd 4th ≥5th

40

92

62

1

64

22

0

11

18

0 6 10

0

7 4 0 4 8

1

Abemaciclib + Al

Abemaciclib + Fulvestrant

Abemaciclib + Other

0

20

60

80

100

Spain Number of patients

Treatment line

Total 1st 2nd 3rd 4th ≥5th

40

97

68

15

56

33

3

11 14

7

16

8 3 4 5 0

10 8

2

Abemaciclib + Al

Abemaciclib + Fulvestrant

Abemaciclib + Other

0

20

60

80

100

Italy Number of patients

Treatment line

Total 1st 2nd 3rd 4th ≥5th

40

100

79

48

62

34

12 9 4 7

0 2 1

Abemaciclib + Fulvestrant

Abemaciclib + Al

A

B

C

Figure 3. Combination therapies with abemaciclib by treatment line in France (A), Italy (B) and Spain (C). Other combination therapies

in France include leuprorelin. Other combination therapies in Spain include 5-fluorouracil, goserelin, tamoxifen or denosumab in

different combinations. Percentages specific to data presented in this figure are outlined within the body of the text. Percentages were

calculated with a total of 155 for France, 181 for Italy and 186 for Spain. In Italy, one patient received abemaciclib as monotherapy and

one patient received other combination therapy with abemaciclib. In Spain, six patients received abemaciclib as monotherapy.

AI: Aromatase inhibitor.

1.7 and 12.9%) therapy lines in France, Italy and Spain,

respectively (Figure 2A–C).

In France and Spain, abemaciclib was mostly prescribed with aromatase inhibitors (AI), such as anastrozole, letrozole and exemestane, (n = 92 [59.4%] and

n = 97 [52.2%], respectively); while in Italy, abemaciclib

was mostly prescribed with fulvestrant (n = 100 [55.2%],

Figure 3). In the first-line, abemaciclib was prescribed with

AI (41.3, 34.3 and 30.1%), followed by fulvestrant (14.2,

26.5 and 17.7%) in France, Italy and Spain, respectively

(Figure 3A–C).

Alist oftreatmentsreceived prior and post abemaciclib

treatment are shown in Supplementary Table S2.

3.4. Abemaciclib dosage

Across the three countries, the proportion of patients

receiving a starting dose of 150 mg bid wassimilar: 85.7%

(n = 126), 88.4% (n = 153) and 86.0% (n = 148) of

patientsin France, Italy and Spain, respectively (Figure 1I).

Dose reductions were also found to be similar: 72 (51.4%)

FUTURE ONCOLOGY 7

A B C

0

20

60

40

21

(17.8%)

45

(38.1%)

32

(27.1%)

20

(17.0%)

Complete response

Number of patients

France Italy Spain

Partial response

Stable disease

Progressive disease

Complete response

Partial response

Stable disease

Progressive disease

Complete response

Partial response

Stable disease

Progressive disease

0

20

60

40

9

(10.8%)

29

(34.9%)

30

(36.1%)

15

(18.1%) Number of patients

0

20

60

40

10

(8.1%)

43

(34.7%)

52

(41.9%)

19

(15.3%) Number of patients

Figure 4. Real-world best overall treatment response according to the RECIST criteria (when available) for patients from France (A), Italy

(B) and Spain (C). For patients with no RECIST criteria collected, best treatment response was provided by the physician’s assessment.

Best treatment response was unknown, not assessed, or too soon to tell for 33 patients from the French cohort, 90 patients from the

Italian cohort and 51 patients from the Spanish cohort. Percentages were calculated with a total of 118 for France, 83 for Italy and 124

for Spain.

RECIST: Response evaluation criteria in solid tumor.

patients in France, 91 (53.2%) patients in Italy and 83

(48.5%) patients in Spain.

3.5. Treatment discontinuation

In France, 45.0% of patients discontinued abemaciclib during the study, while 55.0% were censored. The

median drug survival time for patients from France was

22.0 months(95% CI: 16.8–25.9). In Italy, 33.5% of patients

discontinued abemaciclib during the study, while 66.5%

were censored. The median drug survivaltime for patients

from Italy was 25.8 months (95% CI: 21.0–not reached

[NA]). In Spain, 55.0% of patients discontinued abemaciclib during the study, while 45.0% were censored. The

median drug survival time for patients from Spain was

15.3 months (95% CI: 11.1–18.0).

3.6. Real-world best tumor response

Real-world tumor response assessed by the RECIST criteria was available for 28 patients in France, 77 patients

in Italy and 72 patients in Spain only. Real-world tumor

response assessed by both physician’s judgement and

RECIST criteria (when available) was reported for 118

patients in France, 83 patients in Italy and 124 patients

in Spain. Real-world partial or complete response was

achieved for 66 (55.9%) patients in France, 38 (45.8%)

patientsin Italy and 53 (42.7%) patientsin Spain (Figure 4).

Stable disease was observed in 32 (27.1%) patients in

France, 30 (36.1%) patientsin Italy and 52 (41.9%) patients

in Spain (Figure 4).

3.7. RwPFS

Median duration of follow-up for PFS was 11.2 monthsfor

France with a minimum time of 0.4 months and a maximum time of 31.6 months. In France, median rwPFS was

31.6 months (95% CI: 22.0–31.6) while the 1-year rwPFS

rate was 75.5% (95% CI: 66.3–82.4, Figure 5). After stratification by treatment line, median rwPFS for patients from

France who received abemaciclib in the first, second and

third or more therapy lines was not reached (95% CI:

NA–NA), 23.3 months (95% CI: 14.4–31.6) and 9.0 months

(95% CI: 5.3–25.0), respectively (Figure 5). Additionally,

the 1-year rwPFS rate for patients in France who received

abemaciclib in the first, second and third or more therapy lines was 82.0% (95% CI: 69.6–89.7), 86.8% (95% CI:

64.3–95.6) and 44.0% (95% CI: 23.9–62.4), respectively

(Figure 5).

Median duration of follow-up for PFS was 10.1 months

for Italy with a minimum time of 1.8 months and a maximum time of 32.1 months. In Italy, median rwPFS was

not reached (95% CI: 20.1–NA) while the 1-year rwPFS

rate was 77.2% (95% CI: 68.5–83.8). After stratification

by treatment line, median rwPFS for patients from Italy

who received abemaciclib in the first, second and third

or more therapy lines was not reached (95% CI: NA–NA),

20.0 months (95% CI: 13.0–NA) and not reached (95% CI:

9.6–NA), respectively (Figure 6). Similarly, in Italy, the 1-

year rwPFS rate for patients who received abemaciclib in

the first,second and third or more therapy lineswas 78.7%

8 I. BLANCAS ET AL.

Time from start date of abemaciclib treatment to progression (months)

Patients-at-Risk + Censor

Progression free survival (%)

Treatment line where abemaciclib was received

Patients who received abemaciclib in first-line

Patients who received abemaciclib in second-line

Patients who received abemaciclib since third-line

0

0 6 12 18 24 30 32

First-line

Second-line

≥ Third-line

78

25

31

63

19

17

40

16

7

28

8

4

16

3

4

4

2

1

10

20

30

40

50

60

70

80

90

100

Outcome

Median PFS

1-year PFS

1st line

ΝΑ (ΝΑ-ΝΑ)

82.0 (69.6-89.7)

2nd line

23.3 (14.4-31.6)

86.8 (64.3-95.6)

≥3rd line

9.0 (5.3-25.0)

44.0 (23.9-62.4)

Figure 5. Real-world progression-free survival analysis from abemaciclib initiation to progression in France. Patients were censored at

last dose of abemaciclib. Median rwPFS is presented as months (95% CI). One-year rwPFS rate is presented as % (95% CI). Patients who

were prescribed abemaciclib in >1 treatment line were excluded from this analysis.

(95% CI: 66.7–86.8), 71.4% (95% CI: 50.5–84.7) and 76.0%

(95% CI: 46.9–90.5), respectively (Figure 6).

Median duration of follow-up for PFS was 9.1 months

for Spain with a minimum time of 0.2 months and a

maximum time of 34.2 months. In Spain, overall median

rwPFS was 21.5 months (95% CI: 15.8–NA) while the 1-

yearrwPFS rate was 70.8%(95%CI: 61.5–78.2). Afterstratification by treatmentline, median rwPFS for patientsfrom

Spain who received abemaciclib in the first, second and

third or more therapy lines was 26.0 months (95% CI:

15.8–NA), 20.2 months (95% CI: 7.6–NA) and 15.3 months

(95% CI: 8.7–NA), respectively (Figure 7). Similarly, the 1-

year rwPFS rate for patients from Spain who received

abemaciclib in the first, second and third or more therapy lines was 78.4% (95% CI: 64.6–87.4), 64.5% (95% CI:

36.6–82.6) and 59.1% (95% CI: 41.6–73.0), respectively

(Figure 7).

3.8. Healthcare resource utilization

At least one hospitalization was reported 3 months prior

to abemaciclib initiation for 31 patients from France, 38

patientsfrom Italy and 41 patientsfrom Spain.Conversely,

one or more hospitalization was reported 3 months

after abemaciclib initiation by 19 patients from France, 6

patients from Italy and 26 patients from Spain.

4. Discussion

To our knowledge, our study provides the first real-world

observational data on abemaciclib use in France, Italy and

Spain. Thisstudy hasshowcased patient and clinical characteristics, treatment patterns and outcomes for patients

withHR+/HER2- advanced/metastatic breast cancerfrom

France, Italy and Spain who initiated a treatment regimen that included abemaciclib. An ECOG score of 0 was

FUTURE ONCOLOGY 9

Time from start date of abemaciclib treatment to progression (months)

Patients-at-Risk + Censor

Progression free survival (%)

Treatment line where abemaciclib was received

Patients who received abemaciclib in first-line

Patients who received abemaciclib in second-line

Patients who received abemaciclib since third-line

0

0 6 12 18 24 30 33

First-line

Second-line

≥ Third-line

89

33

21

67

25

15

39

11

9

27

6

7

11

1

3

4

1

0

10

20

30

40

50

60

70

80

90

100

Outcome

Median PFS

1-year PFS

1st line

ΝΑ (ΝΑ-ΝΑ)

78.7 (66.7-86.8)

2nd line

20.0 (13.0-ΝΑ)

71.4 (50.5-84.7)

≥3rd line

ΝΑ (9.6-ΝΑ)

76.0 (46.9-90.5)

Figure 6. Real-world progression-free survival analysis from abemaciclib initiation to progression in Italy. Patients were censored at last

dose of abemaciclib. Median rwPFS is presented as months (95% CI). One-year rwPFS rate is presented as % (95% CI). Patients who were

prescribed abemaciclib in >1 treatment line were excluded from this analysis.

reported for 44.3% of patients from France, 47.3% of

patients from Spain and the majority (77.5%) of patients

from Italy, which may suggest that patientsincluded from

Italy had a better performance status at treatment initiation. Ki-67 index, reported as high or low by physicians, were predominantly high for patients from Italy

and low for patients from France and Spain. Other demographic and clinical characteristics were similar across

the three countries. This real-world population generally presented with a relatively less favorable prognosis as the majority of patients had prior/perioperative

therapies including chemotherapy and radiotherapy and

worse performance status score compared with patients

with advanced/metastatic breast cancer from the abemaciclib clinical trials MONARCH 2 and MONARCH 3 who

were heavily pre-treated and who had no prior systemic

therapy, respectively [14,15].

Overall, more than 85% of patients who initiated abemaciclib in the three countries had a starting dose of

150 mg twice a day, aligning with the abemaciclib label

in the EU [24]. Similar to prior abemaciclib clinical trial

programmes, in the current study, approximately half of

patients across the three countries had a dose reduction [13]. Abemaciclib was mostly prescribed in combination with AI closely followed by fulvestrant in France

and Spain. Conversely, in Italy, abemaciclib was mostly

prescribed in combination with fulvestrant followed by

AI, aligning with prior US-based abemaciclib real-world

findings[20]. The choice of endocrine therapy (aromatase

inhibitor or fulvestrant) across the countries could be

reflective of country-specific prescription patterns orlevel

of adaptation of treatment guidelines by physicians during the study period, though this is speculative and warrantsfurtherinvestigation. PriorUS-based real-world abe-

10 I. BLANCAS ET AL.

Time from start date of abemaciclib treatment to progression (months)

Patients-at-Risk + Censor

Progression free survival (%)

Treatment line where abemaciclib was received

Patients who received abemaciclib in first-line

Patients who received abemaciclib in second-line

Patients who received abemaciclib since third-line

0

0 6 12 18 24 30

First-line

Second-line

≥ Third-line

79

22

49

53

13

30

33

8

18

18

5

11

7

0

7

0

1

10

20

30

40

50

60

70

80

90

100

Outcome

Median PFS

1-year PFS

1st line

26.0 (15.8-ΝΑ)

78.4 (64.4-87.4)

2nd line

20.2 (7.6-ΝΑ)

64.5 (36.6-82.6)

≥3rd line

15.3 (8.7-ΝΑ)

59.1 (41.6-73.0)

Figure 7. Real-world progression-free survival analysis from abemaciclib initiation to progression in Spain. Patients were censored at

last dose of abemaciclib. Median rwPFS is presented as months (95% CI). One-year rwPFS rate is presented as % (95% CI). Patients who

were prescribed abemaciclib in >1 treatment line were excluded from this analysis.

maciclib data reported that 41.2% of patients achieved

partial or complete response, with tumor response based

on the treating clinician’s assessment as reported in the

patient chart [20]. The current study demonstrated that

55.9%of patientsfrom France, 45.8%of patientsfrom Italy

and 42.7% of patientsfrom Spain achieved partial or complete response, demonstrating an overall favorable realworld response following abemaciclib treatment. In the

currentstudy, median rwPFSwas≥20 monthsfor patients

who received abemaciclib in first and second therapy

lines across the three countries while the 1-year rwPFS

rate was >70%, aligning with the rwPFS rate of 61.7%

for the US-based population [20]. Despite the unfavorable prognosis at treatmentstart, findingsfrom thisstudy

align with results from the MONARCH 2 and MONARCH 3

studies where partial or complete response was achieved

for 35.2 and 48.2% of all patients, and median PFS was

16.4 months and not reached, respectively [14,15]. Of

note, a large number of patients were censored in first

line compared with later lines within the rwPFS analysis as they were not on the treatment at the date of last

information in the clinical chart meaning these patients

were on treatment for a shorter duration. Thisis observed

for first line therapy as patients usually undertake new

drugs in second and third or more line in advance of

undertaking it in the first line.

Levels of hospitalization remained low, and relatively

constant, in our sample both in the period immediately

before the initiation of abemaciclib and in the period

after. Consequently, we saw no signs for our group of

patients that the initiation of abemaciclib lead to any significant need for inpatient care and further underlinesthe

safety profile of the drug outlined in the clinical trial evidence.

Limitations of the current findings include the retrospective nature of this study capturing real-world data

on abemaciclib via clinical chart reviews. Despite sample heterogeneity, patient characteristics and treatment

FUTURE ONCOLOGY 11

outcomes were similar for patients recruited across multiple centers in France, Italy and Spain. Real-world tumor

response was not assessed by the RECIST criteria for all

patients across the three countries. Moreover, missing

data from clinical charts challenges findings from this

study. For example, real-world tumor response was only

available for 44.5% of patients from Italy. In addition,

the sample of participating hospitals was not randomly

selected, although hospitals were spread across several

regions within each country. In Spain,the inclusion period

wasinitiated prior to the abemaciclib market launch, indicating that some patients in Spain may have been prescribed abemaciclib based on compassionate use and

that patients from Spain were heavily pre-treated. Additionally, while similarities exist between the characteristics of the patient populations described in this study

and those in abemaciclib clinical trials, differences may

exist, given the methodology used in the chart reviews.

Moreover, reasons behind dose reduction, side effects

and ethnicity information were not collected throughout

this study. Finally, reported rwPFS across treatment lines

was not adjusted to previous therapies; however, rwPFS

by treatment line was reported separately. Two patients

in France,six in Italy and six in Spain had slightly lessthan

3 monthsfollow-up (mean 2.5 months) and were included

in the data collection at source. We have subsequently

repeated the analysis excluding those patients and this

had no impact on the results.

This study is the first large-scale real-world study

evaluating abemaciclib treatment for patients with

HR+/HER2- advanced/metastatic breast cancer in routine care in a European population. Abemaciclib treatment showed favorable treatment outcomes across the

three countries, complementing findings from RCTs and

a previous abemaciclib real-world study. Results from

this study can support treatment decisions in routine

care.

5. Conclusion

This was the first study to identify the profile of patients

who received abemaciclib and its efficacy data in routine care in France, Italy and Spain. Acrossthe three countries, included patients had a mean age of approximately

60 years and were predominantly postmenopausal. Abemaciclib was mostly prescribed with a starting dose

of 150 mg twice a day as a first treatment line concomitantly with AI or fulvestrant. Overall, median rwPFS

was ≥20 months and the 1-year rwPFS rate was >70%.

Additionally, partial or complete response was achieved

by over 42.7% of patients. Effectiveness findings from

this real-world retrospective study align with efficacy

data from clinical trials and demonstrate the benefits of

real-world abemaciclib use for patients with HR+/HER2-

advanced/metastatic breast cancer.

Article highlights

Patient & clinical characteristics

• Patients receiving abemaciclib in routine care in France, Italy and

Spain were predominantly postmenopausal with a mean age of

approximately 60 years. Breast cancer histological type at first

diagnosis was predominantly nonspecific invasive carcinoma.

Treatment patterns

• Abemaciclib was mostly prescribed in the first-line setting in

combination with aromatase inhibitors or fulverstrant.

Dosage

• Overall, most patients who initiated abemaciclib received a

starting dose of 150 mg twice a day.

Treatment discontinuation

• Range of discontinuation was between 45 and 55% across the

three countries.

Real world best tumor response & real-world progression free

survival

• Real-world tumor response and rwPFS support the real-world use

of abemaciclib for the treatment of HR+/HER2-

advanced/metastatic breast cancer.

• Median rwPFS was ≥20 months for patients who received

abemaciclib as first and second therapy lines across the three

countries.

• Median rwPFS was highest for patients who received abemaciclib

in the first-line setting.

Healthcare resource utilization

• Levels of hospitalization remained low, and relatively constant, in

the period immediately before treatment initiation and in the

period after.

Conclusion

• Our findings corroborate the effectiveness of real-world

abemaciclib treatment for patients with advanced/metastatic

breast cancer.

Author contributions

I Blancas had substantial contributions to the conception of the

work. I Blancas, G Sleilaty and W Fakhouri had substantial contributionsto the design of the work. I Blancas, J Grosjean, R Pedersini, S Siddi, RS Bayona and LD Mastro had substantial contributions to the acquisition of data for the work. I Blancas, A

Tamma andNChouaki had substantial contributionsto the analysis of data for the work. I Blancas, R Pedersini, S Siddi, RS Bayona, LD Mastro, C Buzzoni, G Sleilaty, A Molero, A Tamma, N

Chouaki, M Atienza, A Emde and W Fakhouri had substantial

contributions to the interpretation of data for the work. I Blancas and W Fakhouri had substantial contributions to the drafting of the work. I Blancas, J Grosjean, R Pedersini, S Siddi, RS

Bayona, LD Mastro, C Buzzoni, G Sleilaty, A Molero, A Tamma,

N Chouaki, M Atienza, A Emde and W Fakhouri had substantial

contributions to the critical revision of the work for important

intellectual content. All authors give final approval of the work

to be published or presented and have participated sufficiently

in the work to agree to be accountable for all aspects ofthe work

in ensuring that questions related to the accuracy or integrity

of any part of the work are appropriately investigated and

resolved.

12 I. BLANCAS ET AL.

Financial disclosure

This work was funded by Eli Lilly and Company and the sponsor provided writing and editorial support for the current

manuscript. C Buzzoni,GSleilaty,A Molero,ATamma,NChouaki,

M Atienza, A Emde and W Fakhouri are employees and minor

shareholders at Eli Lilly and Company. S Siddi is an employee

of Fundació Sant Joan de Déu who conducted the field work

for this research under contract to Eli Lilly and Company Ltd. Eli

Lilly and Company provided funding for grants and contracts

for Isabel Blancas and Lucia del Mastro, honoraria for I Blancas, R Pedersini, RS Bayona and L del Mastro, support for meetings and travel for I Blancas, J Grosjean, R Pedersini, RS Bayona and L del Mastro, consulting fees for Isabel Blancas and L

del Mastro, advisory boards for I Blancas and expert testimony

for RS Bayona. The authors have no other relevant affiliations

or financial involvement with any organization or entity with a

financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those

disclosed.

Competing interests disclosure

I Blancas received grants or contracts from Roche, AstraZeneca,

Agendia and Pfizer, consulting fees from AstraZeneca, BristolMyers Squibb, Celgene,Daiichi Sankyo, Eisai,Gilead,Grünenthal,

MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen and Veracyte,

honoraria from AstraZeneca, Bristol-Myers Squibb, Celgene,Daiichi Sankyo, Eisai, Gilead, Grünenthal, MSD, Novartis, Pfizer,

Pierre-Fabre, Roche, Seagen and Veracyte, support for meetings and travel from AstraZeneca, Bristol-Myers Squibb, Daiichi

Sankyo, Novartis, Pfizer, Pierre-Fabre and Roche and for advisory boards from AstraZeneca, Bristol-Myers Squibb, Celgene,

Daiichi Sankyo, Eisai, Gilead, Grünenthal, MSD, Novartis, Pfizer,

Pierre-Fabre, Roche, Seagen and Veracyte. J Grosjean received

honoraria from Pfizer,Janssen, Gilead and AstraZeneca and support for attending meetings and travel from Pfizer, AstraZeneca

and Janssen. R Pedersini received honoraria from Gilead, Daichi

Sankyo, Amgen, Sandoz, Novartis, Roche, Dompè, Gentili and

Eisai and support for attending meetings and travel from Gilead

and Roche. S Siddi is an employee of Fundació SantJoan deDéu.

RS Bayona received honoraria from Novartis, Pfizer,AstraZeneca,

Glaxo Smith Kline and Seagen, payments for expert testimony

from Pfizer, AstraZeneca and Novartis, support for attending

meetings and travel from Pfizer, AstraZeneca and Novartis and

had leadership or fiduciary role as ESMO Young Oncologists

Committee member and as the Scientific Secretary of the Spanish Society of Medical Oncology. L Del Mastro received grants

and contracts from, Novartis, Roche, Daiichi Sankyo, Seagen,

Gilead and AstraZeneca, consulting fees from, Gilead, Daiichi

Sankyo and Pierre Fabre, honoraria from Roche, Novartis, Pfizer,

AstraZeneca, Merck Sharp and Dohme, Saegen, Gilead, Pierre

Fabre, Eisai, Exact Sciences, Ipsen, Agendia, Menarini Stemline,

Daiichi Sankyo and GSK, and support for attending meetings

and travel from Roche, Pfizer, Daiichi Sankyo and AstraZeneca.

The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter

or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

C Sirafim, an employee of Eli Lilly and company, provided writing

and editorial assistance for this manuscript.

Ethical conduct of research

For France, the verbal or written non-opposition to use their

data aligning with observational study requirements in France

was obtained from all included patients (Number of declaration: Référence CNIL: 2219942 v 0, study name: Étude

observationnelle de patientes atteintes d’un cancer du sein

HR+/HER2- avancé/mestastatique (aBC/mBC) et traitées par

Abemaciclib. Examen des dossiers médicaux). Ethical approval

has been obtained in Spain from the CEIM/CEI Provincial de

Granada/Junta de Andalucía: 11/01/2021 and from Ethic Committees of each clinicalsatellite site; and in Italy from CER Liguria:

340/2021 - DB id 11165 and from Ethic Committees of each clinicalsatellite sites. In the case of Italy and Spain, written informed

consent was obtained for all patients or the exemption from

patient consent when allowed.

Institutional review boards in Italy consisted of Comitato

Etico Interaziendale A.O.U “Maggiore della Carità” Novara (CE

264/21), Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana/Area Vasta Centro (20671_OSS),

Comitato Etico di Brescia-ASST Spedali Civili (NP 5056), Comitato Indipendente di Etica Medica-ASL Brindisi (CE 224/21_Prot.

100232), Comitato Etico Regionale Liguria (340/2021-DB id

11165), Comitato Etico per la Sperimentazione Clinica delle

Provincie di Treviso e Belluno (1118/CE Marca Trevigiana), Comitato Etico IRCCS Pascale (Prot. 50/21 OSS) and Comitato Etico

Policnico Gemelli (Prot. ID 4566). In Italy, informed consent

was obtained for all patients, except for those exempted due

to the death of participants or if patient is not reachable. In

France, the institutional review board consisted of Commission nationale de l’informatique et des libertés (2219942 v 0)

where the (verbal / non-verbal) non-opposition of the patients

included in the study to the use of their data was obtained.

The exemption from patient consent when allowed, as the

death of participants. In Spain, institutional review boards consisted of CEIM/CEI Provincial de Granada/Junta de Andalucía

(11/01/2021), CEIm de Albacete (2021-07 (EPA-OD)), Hospital

Universitario Ramón y Cajal (03/08/2021), Comité de Ética de

la Investigación con medicamentos Hospital 12 de Octubre

(21/096), Comité de Ética de la Investigación con medicamentos Consorci Hospitalari Provincial de Castelló (28/07/2021) and

Comité de Ética de la Investigación con medicamentos Fundació

Sant Joan de Déu (EOM-01-21 14/01/2021). In Spain, informed

consent was obtained from all patientsto whom the waiver conditions did not apply. The exemption conditionsincluded death

of a participant and the person in charge of data entry is external

to the research team.

Previous presentations

Presented at: Associazione Italiana di Oncologia Medica - 25th

Congresso Nazionale, 10–12 November 2023, Rome, Italy (D38),

International and FrenchOncologyDays, 14–16 June 2023, Paris,

France (AB365) and the 13th European Breast Cancer Conference, 16–18 November 2022, Barcelona, Spain (PB-096) [25–27].

FUTURE ONCOLOGY 13

ORCID

Isabel Blancas https://orcid.org/0000-0002-5867-6615

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