Clinical trial NCT02477644: Platine, Avastin and OLAparib in 1st Line
Official title: Randomized, Double-Blind, Phase III Trial Olaparib vs. Placebo Patients With Advanced FIGO Stage IIIB-IV High Grade Serious or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer Treated Standard First-Line Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: Advanced FIGO IIIB
IV high grade serious ovarian cancer
endometrioid ovarian cancer
standard first-line treatment
platinum-taxane chemotherapy
bevacizumab
olaparib
placebo
Lead sponsor: Arcagy Research
Sponsor class: OTHER
Collaborators: name: Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany
name: Arbeitsgemeinschaft Gynaekologische Onkologie Austria
name: Grupo Español de Investigación en Cáncer de Ovario
name: Belgian Gynaecological Oncology Group
name: Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies
name: Mario Negri Gynecologic Oncology group (MaNGO)
name: Nordic Society of Gynaecological Oncology - Clinical Trials Unit
name: Gynecologic Oncology Trial & Investigation Consortium
First posted: 2015-06-23
Enrollment: 806
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB - IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance.

Detailed description: Patients with advanced FIGO stage IIIB - IV high grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment, combining platinum-taxane chemotherapy and bevacizumab concurrent with chemotherapy and in maintenance.

Eligibility criteria: Inclusion Criteria:

I-1. Female Patient must be ≥18 years of age. I-2. Signed informed consent and ability to comply with treatment and follow-up.

I-3. Patient with newly diagnosed I-3-1 Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer,

I-3-2 Histologically confirmed (based on local histopathological findings):

* high grade serous or
* high grade endometrioid or
* other epithelial non mucinous ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation I-3-3 at an advanced stage: FIGO stage IIIB, IIIC, or IV of the 1988 FIGO classification.

I-4. Patient who has completed prior to randomization first line platinum-taxane chemotherapy:

1. Platinum-taxane based regimen must have consisted of a minimum of 6 treatment cycles and a maximum of 9. However if platinum based therapy must be discontinued early as a result of non hematological toxicity specifically related to the platinum regimen, (i.e. neurotoxicity, hypersensitivity etc.), patient must have received a minimum of 4 cycles of the platinum regimen.
2. Intravenous, intraperitoneal, or neoadjuvant platinum based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle. Interval debulking is allowed.

I-5. Patient must have received prior to randomization a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to realize only 2 cycles of bevacizumab in combination with the last 3 cycles of platinium-based chemotherapy. Bevacizumab treatment should be administered at a dose 15mg/kg q3 weeks up to a total of 15 months.

I-6. Patient must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) from her first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout her first line treatment and prior to study randomization.

I-7. Patient must be randomized at least 3 weeks and no more than 9 weeks after her last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from the previous chemotherapy must have resolved to CTC AE grade 1 or better (except alopecia and peripheral neuropathy).

I-8. Patient must have normal organ and bone marrow function:

1. Hemoglobin ≥ 10.0 g/dL.
2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
3. Platelet count ≥ 100 x 109/L.
4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN.
6. Serum creatinine ≤ 1.25 x institutional ULN and creatinine clearance \> 50 mL/min.
7. Patient not receiving anticoagulant medication who has an International Normalized Ratio (INR) ≤1.5 and an Activated ProThrombin Time (aPTT) ≤1.5 x ULN.

   The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or APTT is within therapeutic limits (according to site medical standard). If the patient is on oral anticoagulants, dose has to be stable for at least two weeks at the time of randomization.
8. Urine dipstick for proteinuria \< 2+. If urine dipstick i s ≥2+, 24-hour urine must demonstrate \<1 g of protein in 24 hours.
9. Normal blood pressure or adequately treated and controlled hypertension (systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg).

I-9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. I-10. Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be available for central BRCA testing and test result must be available for stratification.

I-11. Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. (see appendix 4) I-12. For France only: In France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

E-1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).

E-2. Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma.

E-3. Patient with synchronous primary endometrial cancer unless both of the following criteria are met:

1. stage \< II,
2. Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade III endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1 or 2 endometrioid adenocarcinoma.

Patient with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium is not eligible.

E-4. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS). Patient with a history of localized malignancy diagnosed over 5 years ago may be eligible provided she completed her adjuvant systemic therapy prior to randomization and that the patient remains free of recurrent or metastatic disease.

Patient with history of primary triple negative breast cancer may be eligible provided she completed her definitive anticancer treatment more than 3 years ago and she remains breast cancer disease free prior to start of study treatment.

E-5. Patient with myelodysplastic syndrome/acute myeloid leukemia history E-6. Patient having experienced for at least one cycle, a delay \> 2 weeks due to prolonged hematological recovery during the first line chemotherapy E-7. Patient receiving radiotherapy within 6 weeks prior to study treatment E-8. Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery E-9. Previous allergenic bone marrow transplant. E-10. Any previous treatment with PARP inhibitor, including olaparib. E-11. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics).

E-12. Current or recent (within 10 days prior to randomization) chronic use of aspirin \> 325 mg/day.

E-13. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.

E-14. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.

E-15. Clinically significant (e.g. active) cardiovascular disease, including:

1. Myocardial infarction or unstable angina within ≤ 6 months of randomization,
2. New York Heart Association (NYHA) ≥ grade 2congestive heart failure (CHF).
3. Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG,
4. Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living \[ADL\] requiring repair or revision).

E-16. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.

E-17. History or evidence of hemorrhagic disorders within 6 months prior to randomization.

E-18. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation).

E-19. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.

E-20. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).

E-21. Significant traumatic injury during 4 weeks prior to randomization. E-22. Non-healing wound, active ulcer or bone fracture. Patient with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection is eligible but require 3 weekly wound examinations.

E-23. History of VEGF therapy related abdominal fistula or gastrointestinal perforation or active gastrointestinal bleeding within 6 months prior to the first study treatment.

E-24. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease.

E-25. Patient with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.

E-26. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.

E-27. Pregnant or lactating women. E-28. Participation in another clinical study with an investigational product during her chemotherapy course immediately prior to randomization.

E-29. Patient unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication.

E-30. Patient with a known hypersensitivity to olaparib or any of the recipients of the product.

E-31. Immunocompromised patient, e.g., with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids or patient who is known to be serologically positive for human immunodeficiency virus (HIV).

Primary outcomes:
measure: Efficacy by progression free survival (PFS1)
timeFrame: phase up to a total of 15 months
Secondary outcomes:
measure: Overall survival
timeFrame: Study end
measure: Time to earliest progression by RECIST or CA-125
timeFrame: Study end
measure: Second Progression Free Survival (PFS2)
timeFrame: Study end
measure: Time to start of first subsequent therapy or death (TFST)
timeFrame: Study end
measure: Time to start of second subsequent therapy or death (TSST)
timeFrame: Study end
measure: Safety and Tolerability
timeFrame: Study end
measure: Patient reported outcome
timeFrame: 2 years after last patient included
Other outcomes:
Locations:
city: Graz
country: Austria
facility: KH der Barmherzigen Brüder Graz
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Krankenhaus Hietzing
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Liège
country: Belgium
facility: Hôpital de la Citadelle
city: Namur
country: Belgium
facility: Clinique et maternité Sainte Elisabeth
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
state: Ilhe De France
city: Angers
country: France
facility: ICO Paul Papin
city: Avignon
country: France
facility: Institut Sainte-Catherine
city: Besancon
country: France
facility: Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste de Grenoble
city: La Roche-sur-yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: La Tronche
country: France
facility: Hôpital Michallon - Centre Hospitalier Universitaire de Grenoble
city: Le Mans
country: France
facility: Centre Jean Bernard - Clinique Victor Hugo
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille - Hôpital Huriez
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Mont-de-marsan
country: France
facility: Hôpital de Mont-de-Marsan
city: Montpellier
country: France
facility: ICM Val d'Aurelle
city: Mougins
country: France
facility: Centre Azuréen de Cancérologie
city: Nantes
country: France
facility: Centre Catherine de Sienne - Group confluent
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orleans
country: France
facility: Centre Hospitalier Régional d'Orléans
city: Paris
country: France
facility: Institut Curie - Hopital Claudius Régaud
city: Paris
country: France
facility: Hôpital des Diaconesses
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Groupe Hospitalier Saint-Joseph
city: Perigueux
country: France
facility: Clinique Francheville
city: Pierre-benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Plérin
country: France
facility: Centre CARIO - HPCA
city: Poitiers
country: France
facility: Hôpital de la Milétrie - CHU de Poitiers - Pôle Régional de Cancérologie
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-cloud
country: France
facility: Hôpital René Huguenin, Institut Curie
city: Saint-herblain
country: France
facility: ICO Centre René Gauducheau
city: Strasbourg
country: France
facility: Centre de Radiothérapie - Clinique Sainte-Anne
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Toulouse
country: France
facility: Clinique Pasteur - ONCOSUD
city: Vandoeuvre-les-nancy
country: France
facility: ICL Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Aschaffenburg
country: Germany
facility: Klinikum Aschaffenburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Bad Homburg
country: Germany
facility: Hochtaunus-Kliniken
city: Berlin
country: Germany
facility: Praxisklinik Krebsheilkunde für Frauen
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CVK)
city: Bottrop
country: Germany
facility: Onkologie Bottrop
city: Bremen
country: Germany
facility: GYNAEKOLOGICUM Bremen
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Düsseldorf
country: Germany
facility: Evangelisches Krankenhaus Düsseldorf
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Universitätsfrauenklinik Erlangen
city: Essen
country: Germany
facility: Kliniken Essen Mitte
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst
city: Freiburg
country: Germany
facility: Universitätsfrauenklinik Freiburg
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Göttingen
country: Germany
facility: Universitäts-Frauenklinik Göttingen
city: Gütersloh
country: Germany
facility: Klinkum Gütersloh
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Albertinen Krankenhaus
city: Hannover
country: Germany
facility: Gynäkologisch-Onkologische Praxis Hannover
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Konstanz
country: Germany
facility: Klinikum Konstanz
city: Krefeld
country: Germany
facility: HELIOS Klinikum Krefeld
city: Köln
country: Germany
facility: Universitätsfrauenklinik Köln
city: Köln
country: Germany
facility: St. Elisabeth Krankenhaus
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg
city: Minden
country: Germany
facility: Johannes Wesling Klinikum
city: München
country: Germany
facility: Klinikum der Universität München
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Neumarkt
country: Germany
facility: Kliniken des Landkreises Neumarkt
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach
city: Offenburg
country: Germany
facility: Ortenau Klinikum
city: Ravensburg
country: Germany
facility: Onkologie Ravensburg
city: Regensburg
country: Germany
facility: Universitätsfrauenklinik Regensburg
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg
city: Rosenheim
country: Germany
facility: ROMed Klinikum Rosenheim
city: Rostock
country: Germany
facility: Klinikum Südstadt
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Tübingen
country: Germany
facility: Universitäts-Frauenklinik Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wiesbaden
country: Germany
facility: HELIOS Dr. Horst Schmidt Kliniken
city: Witten
country: Germany
facility: Marien Hospital Witten
city: Wolfsburg
country: Germany
facility: amO Wolfsburg
city: Worms
country: Germany
facility: Klinikum Worms
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi
city: Brescia
country: Italy
facility: Spedali Civili-Università di Brescia
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
city: Genova
country: Italy
facility: EO Ospedali Galliera
city: Lucca
country: Italy
facility: Ospedale San Luca
city: Milano
country: Italy
facility: Istituto Nazionale Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - IRCCS Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Pisa
country: Italy
facility: Ospedale Santa Chiara
city: Prato
country: Italy
facility: AO ASL 4 - Ospedale di Prato
city: Reggio Emilia
country: Italy
facility: Arcispedale S. M. Nuova
city: Roma
country: Italy
facility: Istituto Regina Elena
city: Roma
country: Italy
facility: Policlinico Umberto I La Sapienza
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
city: Torino
country: Italy
facility: Ospedale S. Anna
city: Torino
country: Italy
facility: Ospedale Mauriziano
city: Trento
country: Italy
facility: Ospedale Santa Chiara
city: Ehime
country: Japan
facility: Ehime University Hospital
city: Hyogo
country: Japan
facility: Hyogo Cancer Center
city: Ibaraki
country: Japan
facility: University of Tsukuba Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Medical And Dental Hospital
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Monaco
country: Monaco
facility: Centre Hospitalier Princesse Grace
city: Alcorcón
country: Spain
facility: H. U. Fundación Alcorcón
city: Barcelona
country: Spain
facility: H. de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: C.S. Parc Taulí
city: Córdoba
country: Spain
facility: H. U. Reina Sofía
city: Lleida
country: Spain
facility: H.U. Arnau de Vilanova
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: H. U. Ramón y Cajal
city: Madrid
country: Spain
facility: H. U. 12 de Octubre
city: Oviedo
country: Spain
facility: H.U. Central de Asturias
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Valencia
country: Spain
facility: H. General Universitario de Valencia
city: Valencia
country: Spain
facility: H. U. P. La Fe
city: València
country: Spain
facility: Instituto Valenciano de Oncología
city: Zaragoza
country: Spain
facility: H. U. Miguel Servet
city: Linköping
country: Sweden
facility: Linköping University Hospital
Study officials:
affiliation: Centre Leon Berard
name: Isabelle RAY COQUARD, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ray-Coquard I, Pautier P, Pignata S, Perol D, Gonzalez-Martin A, Berger R, Fujiwara K, Vergote I, Colombo N, Maenpaa J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marme F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. doi: 10.1056/NEJMoa1911361.
citation: Gonzalez-Martin A, Desauw C, Heitz F, Cropet C, Gargiulo P, Berger R, Ochi H, Vergote I, Colombo N, Mirza MR, Tazi Y, Canzler U, Zamagni C, Guerra-Alia EM, Levache CB, Marme F, Bazan F, de Gregorio N, Dohollou N, Fasching PA, Scambia G, Rubio-Perez MJ, Milenkova T, Costan C, Pautier P, Ray-Coquard I; PAOLA1/ENGOT-ov25 investigators. Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial. Eur J Cancer. 2022 Oct;174:221-231. doi: 10.1016/j.ejca.2022.07.022. Epub 2022 Sep 5.
citation: Fujiwara K, Fujiwara H, Yoshida H, Satoh T, Yonemori K, Nagao S, Matsumoto T, Kobayashi H, Bourgeois H, Harter P, Mosconi AM, Vazquez IP, Reinthaller A, Fujita T, Rowe P, Pujade-Lauraine E, Ray-Coquard I. Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial. J Gynecol Oncol. 2021 Sep;32(5):e82. doi: 10.3802/jgo.2021.32.e82.