Analysis of the Clinical Experience With Rucaparib in the Rucaparib Access Program (RAP) in Spain - A GEICO Study
Conditions: Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
Sponsor: Grupo Español de Investigación en Cáncer de Ovario

GEICO 87-R: Final Study Report  
V1 of 29 July 2021 
Page 1 of 69 
 
 
 
 
 
 
 
 
 
 
 
 
 
FINAL STUDY REPORT 
 
Title: 
Analysis of the clinical experience with rucaparib in the rucaparib 
access program (RAP) in Spain – A GEICO Study 
 
Study Number: GEICO 87-R 
 
Retrospective, non-interventional (observational) study 
 
Report Version: V1 of 29 July 2021 
Sponsor: Grupo Español de Investigación en Cáncer de Ovario (GEICO) 
 
 
 
 
 
 
Clinical Coordinating Investigator:  
Dr. Alfonso Yubero Esteban – Hospital Clínico Universitario Lozano Blesa  
 
Funding entity:  
Clovis Oncology, Inc.  
 
 
 
The information contained in this document is confidential and cannot be revealed to other persons without the 
written authorization of the Sponsor. 

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Study Information 
Title 
Analysis of the clinical experience with rucaparib in the 
rucaparib access program (RAP) in Spain – A GEICO 
Study 
 
Sponsor 
Grupo Español de Investigación en Cáncer de Ovario 
(GEICO) 
 
Version identifier of the 
final study report 
V1 of 29 July 2021 
Date of last version of 
the final study report 
29 July 2021 
Active substance 
Rucaparib camsylate 
 
Medicinal product 
Rubraca 
 
Marketing authorization 
holder 
Clovis Oncology Ireland Ltd. 
Research question and 
objectives 
This observational study (GEICO 87-R) was performed in 
high-grade ovarian cancer patients treated within the 
rucaparib access program (RAP) in Spain. The aim was to 
better understand rucaparib’s management in real-life 
setting, to optimize future use, considering platinum-
sensitive and platinum-resistant BRCAmut treatment and 
maintenance patients.  
 
Country of study 
Spain 
 
Author 
Patricio Ledesma 
Head of Clinical Operations 
Sofpromed Investigación Clínica, SLU  
CRO appointed by the Sponsor (GEICO) 
 
 
 
 

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TABLE OF CONTENTS 
1. 
Abstract .................................................................................................................... 5 
2. 
List of abbreviations................................................................................................ 8 
3. 
Investigators ............................................................................................................. 9 
4. 
Other responsible parties...................................................................................... 10 
5. 
Milestones ............................................................................................................... 11 
6. 
Rationale and background ................................................................................... 12 
7. 
Research questions and objectives ....................................................................... 13 
8. 
Amendments and updates .................................................................................... 14 
9. 
Research methods .................................................................................................. 15 
9.1 
Study design ..................................................................................................... 15 
9.2 
Setting .............................................................................................................. 15 
9.3 
Subjects ............................................................................................................ 15 
9.4 
Variables .......................................................................................................... 15 
9.5 
Data sources and measurement ........................................................................ 16 
9.6 
Bias .................................................................................................................. 16 
9.7 
Study size ......................................................................................................... 16 
9.8 
Data transformation ......................................................................................... 16 
9.9 
Statistical methods ........................................................................................... 18 
9.9.1 
Main summary measures .......................................................................... 18 
9.9.2 
Main statistical methods ........................................................................... 18 
9.9.3 
Missing values .......................................................................................... 18 
9.9.4 
Sensitivity analyses .................................................................................. 19 
9.9.5 
Amendments to the statistical analysis plan ............................................. 19 
9.10 Quality control ................................................................................................. 19 
10. 
Results ................................................................................................................. 20 
10.1 Participants ....................................................................................................... 20 
10.2 Descriptive data ............................................................................................... 20 
10.3 Outcome data ................................................................................................... 52 
10.4 Main results ...................................................................................................... 56 
10.5 Other analyses .................................................................................................. 56 
10.6 Adverse events/adverse reactions .................................................................... 56 
11. 
Discussion ........................................................................................................... 66 
11.1 Key results ....................................................................................................... 66 

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11.2 Limitations ....................................................................................................... 66 
11.3 Interpretation .................................................................................................... 66 
11.4 Generalisability ................................................................................................ 66 
12. 
Other information ............................................................................................. 67 
13. 
Conclusion .......................................................................................................... 68 
14. 
References........................................................................................................... 69 
 
 
 
 
 

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1. Abstract 
 
Title 
 
Analysis of the clinical experience with rucaparib in the rucaparib access program 
(RAP) in Spain – A GEICO Study 
 
Keywords 
 
Rucaparib, rucaparib access program, ovarian cancer 
 
Rationale and background 
 
Rucaparib is a PARP-1/2/3 inhibitor approved for the treatment of high-grade ovarian 
cancer. In ARIEL3, rucaparib improved progression-free survival (PFS) as maintenance 
therapy for platinum (Pt)-sensitive recurrent ovarian cancer. Study 10, ARIEL2, and 
ARIEL4 showed rucaparib’s benefit as treatment.  
 
Research question and objectives 
 
An observational study (GEICO 87-R) was performed in high-grade ovarian cancer 
patients treated within the rucaparib access program (RAP) in Spain. The aim was to 
better understand rucaparib’s management in real-life setting, to optimize future use, 
considering Pt-sensitive and Pt-resistant BRCAmut treatment and maintenance patients.  
 
Study design 
 
A retrospective study was performed at 22 GEICO hospitals in Spain that treated 
patients within RAP (600 mg BID) since September 2018. Adult women with high-
grade epithelian ovarian, fallopian tube, or primary peritoneal cancer, with medical 
record available, were included. Patient characteristics, medical history, safety, efficacy, 
and dosing data were collected.  
 
Setting 
 
The setting of this observational study was rucaparib’s access program (RAP) in Spain, 
in the context of real-life use of the product. 
 
Subjects and study size, including dropouts 
 
The study recruited adult (18 years or more) women according to the following criteria:  
 
Inclusion criteria:  
 
1.- Written informed consent must be signed by all patients participating in the study who 
can be interviewed in the hospital (accessible, alive patients). Informed consent may not be 
required from unaccesible patients (dead, lost, etc.) according to ethics committee 
permissions and applicable law for retrospective studies in Spain.  
2.- Histological diagnosis of high-grade epithelian ovarian, fallopian tube, or primary 
peritoneal cancer treated in the context of rucaparib access program (RAP) in Spain.  

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3.- Adult women (18 years or more at the time of diagnosis).  
 
Exclusion criteria:  
 
1.- Patients without medical record available (lost, empty or unretrievable clinical 
information).  
 
The study will include up to 70 patients in total (retrospective in all cases). The 
population will include all patients who received at least one dose of rucaparib as part of 
the RAP in GEICO-associated hospitals. The sample size will be based on the accrual 
rate of the RAP and the date of rucaparib launch in Spain. There will be no formal 
calculation of the sample size. All patients included in the RAP between September 
2018 and the date of the rucaparib launch in Spain will be analyzed. 
 
Variables and data sources 
 
 
Patient characteristics and medical history: Sex, age, mutational status (BRCA 1/2 
[germline/somatic] and in other HRR genes), number of previous relapses, number 
of previous chemotherapy regimens, types of treatments received (chemotherapy, 
targeted therapies [bevacizumab, PARPi]), prior maintenance or with maintenance, 
treatment-free interval (platinum-based chemotherapy, non-platinum-based 
chemotherapy, targeted therapy).  
 
Rucaparib safety data: all rucaparib-related hematological and non-hematological, 
serious and non-serious adverse events (grade, start date, end date, action taken with 
rucaparib, outcome); others (GI, HBP, cognitive, and psychological sphere). In 
addition, adverse event treatments will be registered in the study database.  
 
Rucaparib efficacy data: best response rates in the treatment indication patients, 
duration of response and PFS in the treatment indication patients, PFS in the 
maintenance indication patients, radiological response to chemotherapy in 
maintenance patients (and impact of response on patient evolution).  
 
Rucaparib dosing data: mean starting dose, number of dose reductions, reasons for 
reductions, number of treatment discontinuations, reasons for discontinuations, 
duration of treatment, and switching of maintenance therapy to another PARP 
inhibitor (including reasons for switching).  
 
In order to show that data obtained in clinical trials could be reproduced in non-
screened patients, the outcomes will be discussed in the context of the results from 
ARIEL3 trial and the integrated analysis of Study 10 and ARIEL2.  
 
These data are to be obtained from the participating hospitals per local practice (clinical 
records, local reports). 
 
Results 
 
Between July 2020 and February 2021, 51 patients were recruited with median age 63 
years (36-86). At diagnosis, 45.1% of patients harbored gBRCA mutations, 19.6% 
sBRCA mutations, and 31.4% were BRCAwt. Before rucaparib, patients had ECOG 
performance status 0, 1, or 2 (37.3%, 49.0%, and 5.9%) and 72.5% had measurable 
disease. The median number of previous lines was 4 (1-9), 51.0% of patients received 
prior bevacizumab, and notably 25.5% of patients had received a prior PARPi. 
Rucaparib was given as maintenance, Pt-resistant, and Pt-sensitive treatment in 35.3%, 
51.0%, and 13.7% of patients respectively (median dose 550.0 mg [299-600]). 91.3% of 

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patients received rucaparib for ≤12 months and 8.7% >12 months. 50.0% had at least 
one dose reduction and 60.0% at least one dose interruption. 9.8% discontinued due to 
rucaparib toxicity and 5 patients remained on treatment upon analysis. Median PFS was 
6.0 months (95% CI 2.5-7.8). For treatment group (19 radiologically-evaluable pts), the 
disease control rate was 42.0% (21.0% PR and 21.0% SD). Overall, 86.3% of patients 
had rucaparib-related toxicities, while most common G3-4 hematological events were 
anemia (13.7%), neutropenia (5.9%), and thrombocytopenia (5.9%). 
 
Discussion 
 
Rucaparib’s safety profile in real-life setting is manageable and efficacy results, even 
considering heavily pre-treated patients, are comparable to those of previous trials. The 
RAP in Spain showed a consolidated management of rucaparib and, consequently, an 
improved safety profile. 
 
Marketing Authorization Holder 
 
Clovis Oncology Ireland Ltd. 
 
Names and affiliations of principal investigators 
 
1. Alfonso Yubero-Esteban - Hospital Clínico Universitario Lozano Blesa 
2. Arantzazu Barquin - Centro Integral Oncológico Clara Campal  
3. Purificación Estévez - Hospital Universitario Virgen del Rocío  
4. Bella Pajares Hachero - Hospital Universitario Virgen de la Victoria  
5. Luisa Sánchez - Clínica Universidad de Navarra, Madrid  
6. Piedad Reche - Hospital Universitario Torrecárdenas  
7. Jesús Damián Alarcón - Hospital Universitari Son Espases  
8. Julia Calzas - Hospital Universitario de Fuenlabrada  
9. Lydia Gaba - Hospital Clínic de Barcelona  
10. José Fuentes-Pradera - Hospital Universitario Virgen de Valme  
11. Ana Santaballa - Hospital Universitari i Politècnic la Fe  
12. Carmen Salvador - Hospital Lluís Alcanyís de Xàtiva  
13. Luis Manso - Hospital Universitario 12 de Octubre  
14. Ana Herrero-Ibáñez - Hospital Universitario Miguel Servet  
15. Álvaro Taus - Hospital del Mar  
16. Rául Márquez - MD Anderson Cancer Center Madrid  
17. Julia Madani - Hospital Universitario San Jorge  
18. María Merino - Hospital Universitario Infanta Sofía  
19. Gloria Marquina – Hospital Clínico San Carlos  
20. Antonio González-Martín - Clínica Universidad de Navarra, Madrid 
21. Victoria Casado – Fundación Jiménez Díaz 
22. Manuel Constenla – Complejo Hospitalario Universitario de Pontevedra 
23. María Gutiérrez - Hospital Universitario de Araba Txagorritxu 
 
 

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2. List of abbreviations 
 
 AE: Adverse Event 
 BID: bis in die (twice a day) 
 BRCA: Breast Cancer Gene 
 CM: Concomitant Medication 
 CR: Complete Response 
 CRO: Clinical Research Organization 
 DoR: Duration of Response 
 ECOG:  Eastern Cooperative Oncology Group 
 E-CRF: Electronic Case Report Form 
 FDA: Food and Drug Administration 
 GCP: Good Clinical Practice 
 GEICO: Grupo Español de Investigación en Cáncer de Ovario 
 GI: Gastrointestinal 
 HBP: High Blood Pressure 
 HRR: Homologous Recombination Repair 
 ICF: Informed Consent Form 
 KM: Kaplan-Meier 
 LOH: Loss of heterozygosity 
 MH: Medical History 
 ORR: Objective Response Rate 
 PARP: Poly adenosine diphosphate-ribose polymerase 
 PFS: Progression-Free Survival 
 PIS: Patient Information Sheet 
 PR: Partial Response 
 RAP: Rucaparib Access Program 
 RECIST: Response Evaluation Criteria in Solid Tumors 
 SD: Stable Disease 
 SE: Standard Error 
 STD: Standard Deviation 
 

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3. Investigators 
 
1. Alfonso Yubero-Esteban - Hospital Clínico Universitario Lozano Blesa 
2. Arantzazu Barquin - Centro Integral Oncológico Clara Campal  
3. Purificación Estévez - Hospital Universitario Virgen del Rocío  
4. Bella Pajares Hachero - Hospital Universitario Virgen de la Victoria  
5. Luisa Sánchez - Clínica Universidad de Navarra, Madrid  
6. Piedad Reche - Hospital Universitario Torrecárdenas  
7. Jesús Damián Alarcón - Hospital Universitari Son Espases  
8. Julia Calzas - Hospital Universitario de Fuenlabrada  
9. Lydia Gaba - Hospital Clínic de Barcelona  
10. José Fuentes-Pradera - Hospital Universitario Virgen de Valme  
11. Ana Santaballa - Hospital Universitari i Politècnic la Fe  
12. Carmen Salvador - Hospital Lluís Alcanyís de Xàtiva  
13. Luis Manso - Hospital Universitario 12 de Octubre  
14. Ana Herrero-Ibáñez - Hospital Universitario Miguel Servet  
15. Álvaro Taus - Hospital del Mar  
16. Rául Márquez - MD Anderson Cancer Center Madrid  
17. Julia Madani - Hospital Universitario San Jorge  
18. María Merino - Hospital Universitario Infanta Sofía  
19. Gloria Marquina – Hospital Clínico San Carlos  
20. Antonio González-Martín - Clínica Universidad de Navarra, Madrid 
21. Victoria Casado – Fundación Jiménez Díaz 
22. Manuel Constenla – Complejo Hospitalario Universitario de Pontevedra 
23. María Gutiérrez - Hospital Universitario de Araba Txagorritxu 
 
 
 

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4. Other responsible parties 
 
The Sponsor of this study was the Grupo Español de Investigación en Cancer de Ovario 
(GEICO). 
 

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5. Milestones 
 
Milestone 
Planned date 
Actual date 
Comments 
Start of data 
collection 
15 July 2020 
29 July 2020 
 
End of data 
collection 
15 December 2020 
25 May 2021 
Includes data 
cleaning period. 
Delay caused by the 
need of issuing 
additional queries. 
Final report of 
study results 
31 March 2021 
29 July 2021 
 
 
 

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6. Rationale and background 
 
Rucaparib is a small molecule inhibitor of PARP-1, PARP-2, and PARP-3 that has 
demonstrated preclinical and clinical activity in epithelial ovarian cancer with 
deleterious mutations in BRCA1/2 or other HRR gene and/or high level of genomic 
LOH.  
 
Rucaparib was approved by the U.S. FDA in December 2016 for the treatment of 
patients with advanced ovarian cancer with BRCA mutation (germline and/or somatic) 
who have been treated with two or more chemotherapies (1, 2). Rucaparib approval was 
based on the proportion of patients with an observed objective response in a pooled 
population of patients with BRCA-mutated high-grade ovarian carcinoma from clinical 
studies Study 10 and ARIEL2 (3, 4).  
 
More recently, the results of the Phase 3 ARIEL3 clinical trial demonstrated that 
rucaparib improves PFS as maintenance therapy for patients with platinum-sensitive 
recurrent ovarian cancer (5).  
 
An additional Phase 3 clinical trial, ARIEL4, is currently enrolling patients with 
relapsed BRCA-mutated high-grade ovarian cancer who have received at least two prior 
chemotherapy regimens (6).  
 
Rucaparib is indicated in Europe:  
 
 As monotherapy for the maintenance treatment of adult patients with platinum-
sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary 
peritoneal cancer who are in response (complete or partial) to platinum-based 
chemotherapy.  
 As monotherapy treatment of adult patients with platinum-sensitive, relapsed or 
progressive, BRCA mutated (germline and/or somatic), high-grade epithelial 
ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with 
two or more prior lines of platinum-based chemotherapy, and who are unable to 
tolerate further platinum-based chemotherapy.  
 
The Rucaparib Access Program (RAP) currently provides the drug for these licensed 
indications. In addition, the RAP also provides rucaparib as off-label use for patients 
with a special clinical need which cannot be satisfied by a licensed medication: Patients 
with relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade 
epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated 
with two or more prior lines of platinum-based chemotherapy, and who are currently 
platinum-resistant and require treatment with rucaparib.  
 
This program has been active in Spain since September 2018. More than 60 patients 
have been included until now.  
 
An observational study (GEICO 87-R) was proposed in high-grade ovarian cancer 
patients treated within the rucaparib access program (RAP) in Spain. The aim was to 
better understand rucaparib’s management in real-life setting, to optimize future use, 
considering platinum-sensitive and platinum-resistant BRCAmut treatment and 
maintenance patients.  

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7. Research questions and objectives 
 
The general aim of this study was to better understand and optimize rucaparib’s future 
clinical management in patients with high-grade epithelian ovarian, fallopian tube, or 
primary peritoneal cancer treated in the context of rucaparib access program (RAP) in 
Spain.  
 
To this end, a clinical database was built including clinical data in three scenarios of 
rucaparib treatment: (1) platinum-sensitive BRCA-mutated patients after progression, 
(2) maintenance therapy in patients after a platinum-sensitive relapse in response, and 
(3) treatment therapy in BRCA-mutated patients who were platinum-resistant.  
 
The specific objectives of the study were:  
 
 To describe patient characteristics/medical history, safety, efficacy, and dosing 
of on-label treatment with rucaparib in real-world patients (real-world data).  
 To describe patient characteristics/medical history, safety, efficacy, and dosing 
of all patients treated with rucaparib (including patients with on-label treatment 
and others) in real-world patients (real-world data).  
 To show that data obtained in clinical trials could be reproduced in non-screened 
patients.  
 
 

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8. Amendments and updates 
 
No amendments were performed to the study protocol. 
 

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9. Research methods 
 
9.1 Study design 
 
The study consisted of a retrospective observational, multicenter study in which the 
fundamental exposure factor being investigated was a drug (rucaparib). The study was 
developed at national level with the initial intention of including nearly 27 sites in 
Spain, during a data collection period of 3 months. 
 
9.2 Setting 
 
The setting of this observational study was rucaparib’s access program (RAP) in Spain, 
in the context of real-life use of the product. 
 
9.3 Subjects 
 
The study recruited adult (18 years or more) women according to the following criteria:  
 
Inclusion criteria:  
 
1.- Written informed consent must be signed by all patients participating in the study who 
can be interviewed in the hospital (accessible, alive patients). Informed consent may not be 
required from unaccesible patients (dead, lost, etc.) according to ethics committee 
permissions and applicable law for retrospective studies in Spain.  
2.- Histological diagnosis of high-grade epithelian ovarian, fallopian tube, or primary 
peritoneal cancer treated in the context of rucaparib access program (RAP) in Spain.  
3.- Adult women (18 years or more at the time of diagnosis).  
 
Exclusion criteria:  
 
1.- Patients without medical record available (lost, empty or unretrievable clinical 
information).  
 
9.4 Variables 
 
 
Patient characteristics and medical history: Sex, age, mutational status (BRCA 1/2 
[germline/somatic] and in other HRR genes), number of previous relapses, number 
of previous chemotherapy regimens, types of treatments received (chemotherapy, 
targeted therapies [bevacizumab, PARPi]), prior maintenance or with maintenance, 
treatment-free interval (platinum-based chemotherapy, non-platinum-based 
chemotherapy, targeted therapy).  
 
Rucaparib safety data: all rucaparib-related hematological and non-hematological, 
serious and non-serious adverse events (grade, start date, end date, action taken with 
rucaparib, outcome); others (GI, HBP, cognitive, and psychological sphere). In 
addition, adverse event treatments will be registered in the study database.  
 
Rucaparib efficacy data: best response rates in the treatment indication patients, 
duration of response and PFS in the treatment indication patients, PFS in the 
maintenance indication patients, radiological response to chemotherapy in 
maintenance patients (and impact of response on patient evolution).  
 
Rucaparib dosing data: mean starting dose, number of dose reductions, reasons for 
reductions, number of treatment discontinuations, reasons for discontinuations, 

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duration of treatment, and switching of maintenance therapy to another PARP 
inhibitor (including reasons for switching).  
 
In order to show that data obtained in clinical trials could be reproduced in non-
screened patients, the outcomes will be discussed in the context of the results from 
ARIEL3 trial and the integrated analysis of Study 10 and ARIEL2.  
 
9.5 Data sources and measurement 
 
The data collected in this study included family history characteristics, clinical-pathological 
features of the tumor, treatment approaches, and long-term outcomes. These data were 
obtained from the participating hospitals per local practice (clinical records, local reports).  
 
9.6 Bias 
 
Since this was a retrospective observational study, no sources of bias were identified. 
 
9.7 Study size 
 
The study initially planned to include up to 70 patients in total (retrospective in all 
cases). The population included all patients who received at least one dose of rucaparib 
as part of the RAP in GEICO-associated hospitals. The sample size was based on the 
accrual rate of the RAP and the date of rucaparib launch in Spain. There was no formal 
calculation of the sample size. All patients included in the RAP between September 
2018 and the date of the rucaparib launch in Spain were analyzed. 
 
9.8 Data transformation 
 
Stratification Factors 
 
Data was stratified by age subgroups (<70 years vs ≥70 years).  
 
Patients Characteristics  
 
The information of patients such as age, sex, race and other baseline characteristics 
were summarized.  
 
Exposure  
 
All data collected that was not free text was reported: mean starting dose, number of 
dose reductions, reasons for reductions, number of treatment discontinuations, reasons 
for discontinuations, duration of treatment, and switching of maintenance therapy to 
another PARP inhibitor (including reasons for switching).  
 
Concomitant Medications (CMs) and Medical History (MH)  
 
The CMs were presented in the summary using frequency counts and percentages 
stratified by whether they occurred before or during rucaparib. When summarizing the 
number and percentage of subjects with some concomitant medications, subjects with 
multiple occurrences of the same CM were counted only once.  
 

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In MH all data collected that was not free text was reported: mutational status (BRCA 
1/2 [germline/somatic] and in other HRR genes), number of previous relapses, number 
of previous chemotherapy regimens, types of treatments received (chemotherapy, 
targeted therapies [bevacizumab, PARPi]), prior maintenance or with maintenance, 
treatment-free interval (platinum-based chemotherapy, non-platinum-based 
chemotherapy, targeted therapy).  
 
Initial Ovarian Cancer Diagnosis  
 
The information of initial diagnosis such as age, tumor histology, FIGO stage, and 
mutational status was summarized.  
 
Ovarian Cancer Treatments (Previous Surgeries)  
 
All the data collected was summarized as the number of previous surgeries and time 
from the last previous surgery to rucaparib (categorically and numerically).  
 
Ovarian Cancer Treatments (Previous Systemic Treatments)  
 
All data collected other than free text was reported: total number of previous lines, total 
number of each type of treatment received per patient, time from last previous systemic 
treatment to rucaparib. In addition, the last line prior to rucaparib was listed as well as 
the duration, time passed between the last previous line and rucaparib and time to 
progression. 
 
Progression-Free Survival (PFS)  
 
PFS: Measured in months from the date of the first dose to the date of the first 
progression (PD) (whether radiological, clinical or biological) or to the date of death 
from any cause, whichever occurs first.  
 
Objective Response Rate (ORR)  
 
ORR: Confirmed best overall tumor response of CR or PR according to RECIST v1.1 or 
Response and normalization or Response according to Rustin criteria. The RECIST v1.1 
answer prevailed over the Rustin criterion answer except where RECIST is ‘Not 
assessable’ and Rustin criterion is different than ‘Not assessable’.  
 
ORR was calculated only on the treatment population and not on the maintenance 
population.  
 
Duration of Response (DoR)  
 
DoR: Defined as time in months from date of documentation of tumor response (CR or 
PR) to date of disease progression. DoR was calculated only on the treatment 
population and not on the maintenance population.  
 
The patients were listed indicating the response and the duration of the response in 
months. 
 

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Adverse Events (AEs) 
 
The AEs were presented in the summary using counts and frequency percentages. They 
were stratified by grade and event, by time from rucaparib initiation, grade and event, 
and by event duration, grade and event. The number of events and the number of 
patients and percentage who had that event was indicated.  
 
Clinical Laboratory Evaluations  
 
Laboratory raw variables collected in the baseline visit will be summarized. 
 
9.9 Statistical methods 
 
9.9.1 Main summary measures 
 
All variables were summarized separately. Depending on the type of the variable, the 
following statistics were reported:  
 
 Continuous variables: number of subjects (n), number of missings, mean, 
standard deviation (STD), median, standard error (SE, if needed), 25th and 75th 
percentiles, minimum, and maximum.  
 Categorical variables: frequencies and percentages (calculated over the number 
of non-missing values).  
 
In general, minimum and maximum were reported using the same number of decimal 
places as collected in the raw data. Mean, STD, median, 25th and 75th percentiles were 
reported with one additional decimal place.  
 
9.9.2 Main statistical methods 
 
Time to event data were listed and summarized at every specified timepoint using the 
number patients at risk, number of patients censored, number of patients with the event, 
Kaplan Meier estimate (%), and the 95% confidence interval. In addition, 25th, 50% 
and 75th percentiles from Kaplan-Meier (KM) curves were used. 
 
Time to event data was also represented graphically including KM curves, number of 
patients at risk and the KM medians. Censored patients were only be represented on the 
KM curves (+).  
 
For ORR the rate and corresponding exact binomial confidence intervals were used in 
the analysis. In the calculation of the confidence intervals, PR, CR and SD were taken 
into account as a single category.  
 
For continuous efficacy variables such as PFS, their medians were used. Association 
between variables were measured and tested by conventional statistical analysis: 
Pearson and/or Spearman tests. 
 
9.9.3 Missing values 
 
No imputation of missing data was performed.  

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9.9.4 Sensitivity analyses 
 
Not applicable. 
 
9.9.5 Amendments to the statistical analysis plan 
 
No amendments were made to the initial statistical analysis plan. 
 
9.10 
Quality control 
 
Each study site was subject to remote clinical monitoring and review by the ethics 
committees. 
 
The study data was reviewed and cleaned by periodic inspection of the e-CRFs. Remote 
reviews were performed with enough frequency to ascertain the following:  
 
 Integrity and accuracy of data:  
- 
Informed consent (version, signature and date)  
- 
Eligibility criteria  
 e-CRF completion.  
 Protocol deviations according GCPs and the applicable regulatory local 
requirements. Taking appropriate action to prevent recurrence to the detected 
deviations.  
 Compliance with approved protocol and all approved amendments, if any.  
 That the investigator receives all documents needed to conduct the study 
properly and to comply with the applicable regulations.  
 That the investigator and local staff are adequately informed about the study 
through telephone initiation visits.  
 
The study appointed CRO reviewed the e-CRFs for compliance with the protocol, and 
for inconsistent or missing data. When any missing data or data anomalies were found, 
queries were sent to the relevant center for resolution. Following the required reviews, 
the e-CRF data items were exported into the clinical study database for statistical 
analysis.  
 

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10. Results 
 
10.1 
Participants 
 
The study recruited a total of 51 eligible participants. 
 
10.2 
Descriptive data 
 
 
 

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10.3 
Outcome data 
 
 
 
 
 

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10.4 
Main results 
 
Between July 2020 and February 2021, 51 patients were recruited with median age 63 
years (36-86). At diagnosis, 45.1% of patients harbored gBRCA mutations, 19.6% 
sBRCA mutations, and 31.4% were BRCAwt. Before rucaparib, patients had ECOG 
performance status 0, 1, or 2 (37.3%, 49.0%, and 5.9%) and 72.5% had measurable 
disease. The median number of previous lines was 4 (1-9), 51.0% of patients received 
prior bevacizumab, and notably 25.5% of patients had received a prior PARPi. 
Rucaparib was given as maintenance, Pt-resistant, and Pt-sensitive treatment in 35.3%, 
51.0%, and 13.7% of patients respectively (median dose 550.0 mg [299-600]). 91.3% of 
patients received rucaparib for ≤12 months and 8.7% >12 months. 50.0% had at least 
one dose reduction and 60.0% at least one dose interruption. 9.8% discontinued due to 
rucaparib toxicity and 5 patients remained on treatment upon analysis. Median PFS was 
6.0 months (95% CI 2.5-7.8). For treatment group (19 radiologically-evaluable pts), the 
disease control rate was 42.0% (21.0% PR and 21.0% SD). Overall, 86.3% of patients 
had rucaparib-related toxicities, while most common G3-4 hematological events were 
anemia (13.7%), neutropenia (5.9%), and thrombocytopenia (5.9%). 
 
10.5 
Other analyses 
 
Additional analyses by age groups (less than 70 years vs. 70 years or older) available 
upon request. 
 
10.6 
Adverse events/adverse reactions 
 
 
 

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11. Discussion 
 
11.1 
Key results 
 
 Between July 2020 and February 2021, 51 patients were recruited with median 
age 63 years (36-86).  
 At diagnosis, 45.1% of patients harbored gBRCA mutations, 19.6% sBRCA 
mutations, and 31.4% were BRCAwt.  
 Before rucaparib, patients had ECOG performance status 0, 1, or 2 (37.3%, 
49.0%, and 5.9%) and 72.5% had measurable disease.  
 The median number of previous lines was 4 (1-9), 51.0% of patients received 
prior bevacizumab, and notably 25.5% of patients had received a prior PARPi. 
 Rucaparib was given as maintenance, Pt-resistant, and Pt-sensitive treatment in 
35.3%, 51.0%, and 13.7% of patients respectively (median dose 550.0 mg [299-
600]).  
 91.3% of patients received rucaparib for ≤12 months and 8.7% >12 months. 
 50.0% had at least one dose reduction and 60.0% at least one dose interruption. 
 9.8% discontinued due to rucaparib toxicity and 5 patients remained on 
treatment upon analysis.  
 Median PFS was 6.0 months (95% CI 2.5-7.8).  
 For treatment group (19 radiologically-evaluable pts), the disease control rate 
was 42.0% (21.0% PR and 21.0% SD).  
 Overall, 86.3% of patients had rucaparib-related toxicities, while most common 
G3-4 hematological events were anemia (13.7%), neutropenia (5.9%), and 
thrombocytopenia (5.9%). 
 
11.2 
Limitations 
 
In this study, the following limitations should be considered: 
 
 Heterogeneous population in terms of baseline characteristics (retrospective 
study)  
 Reliance on local testing for germline or somatic mutations  
 Limited follow-up  
 
11.3 
Interpretation 
 
This study demonstrated that rucaparib’s safety profile in real-life setting is manageable 
and efficacy results, even considering heavily pre-treated patients, are comparable to 
those of previous clinical trials. The RAP in Spain showed a consolidated management 
of rucaparib and, consequently, an improved safety profile in the treated patients.  
 
11.4 
Generalisability 
 
The safety and efficacy results of this study are comparable to those of previous clinical 
trials with rucaparib. 
 

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12. Other information 
 
All patients participating in the study (accessible, alive patients who could be 
interviewed in the hospital) received a Patient Information Sheet (PIS) describing, in 
simple language, the goals, scope, procedures and relevant implications of the study.  
 
The PIS integrated an Informed Consent Form (ICF) to be signed by the patient, which 
was indispensable for study participation (for accessible patients).  
 
Written informed consent had to be given by each accessible/reachable patient before 
study initiation (prior to registration of the patient in the e-CRF). The PIS/ICF included 
the consent of patients for the collection and analysis of their clinical data.  
 
Data of unaccesible/unreachable patients (dead, lost, etc.) could still be used according 
to the permissions of ethics committees and Spanish law, regarding the use of data in 
retrospective studies.  
 
 
 

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13. Conclusion 
 
Rucaparib’s safety profile in real-life setting is manageable and efficacy results, even 
considering heavily pre-treated patients, are comparable to those of previous trials. The 
RAP in Spain showed a consolidated management of rucaparib and, consequently, an 
improved safety profile.  
 

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14. References 
 
1. Rucaparib Summary of Product Characteristics (SmPC) 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/004272/WC500249806.pdf  
 
2. Oza AM, Tinker AV, Oaknin A, Shapira-Frommer R, McNeish IA, Swisher EM, et 
al. Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-
grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: 
Integrated analysis of data from Study 10 and ARIEL2. Gynecol Oncol. 2017.  
 
3. Kristeleit R, Shapiro GI, Burris HA, et al. A phase I–II study of the oral PARP 
inhibitor rucaparib in patients with germline BRCA1/2-mutated ovarian carcinoma or 
other solid tumours. Clin Cancer Res 2017; 23: 4095–106.  
 
4. Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-
grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, 
phase 2 trial. Lancet Oncol 2017; 18: 75–87.  
 
5. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, et al. 
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to 
platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 
trial. The Lancet. 2017; 390(10106):1949-1961.  
 
6. Clovis Oncology Data on File March 2nd, 2018.