Clinical trial NCT03353831: Atezolizumab With Bevacizumab and Chemotherapy vs Bevacizumab and Chemotherapy in Early Relapse Ovarian Cancer
Official title: Atezolizumab in Combination With Bevacizumab and Chemotherapy Versus Bevacizumab and Chemotherapy in Recurrent Ovarian Cancer - a Randomized Phase III Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent Ovarian Carcinoma
Keywords: Recurrent Ovarian Cancer
Atezolizumab
Bevacizumab
Lead sponsor: AGO Research GmbH
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2017-11-27
Enrollment: 574
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: This is a phase III, randomized, partially blinded, multicenter trial to evaluate the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy compared to placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian-, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after platinum based chemotherapy or 3rd relapse.

Detailed description: Approximately 550 patients will be randomized in a 1:1 ratio to the treatments as specified below:

Arm A: Chemotherapy + Bevacizumab + Placebo Arm B: Chemotherapy + Bevacizumab + Atezolizumab

Study treatment will continue until disease progression per RECIST v1.1, unacceptable toxicity, or patient or investigator decision to discontinue treatment. Atezolizumab/placebo, chemotherapy and bevacizumab may be discontinued for toxicity independently of each other in the absence of disease progression.

For each patient, chemotherapy (PLD or Paclitaxel weekly) will be selected by the investigator prior to randomization.

Recruitment to an individual chemotherapy cohort will be closed once 50% of patients are recruited to this cohort. In such case the remaining cohort will remain open for recruitment.

Eligibility criteria: Inclusion Criteria:

1. Patients with histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer
2. Relapsed disease
3. Patients with up to three prior therapies. In patients with 1 or 2 prior treatment lines, the treatment free interval after platinum has to be less than 6 months; in addition patients with three prior lines of chemotherapy who are not considered for platinum-containing chemotherapy lines are also eligible
4. Measurable disease, evaluable disease in combination with GCIG CA-125 criteria, or histologically proven relapse/progression
5. Mandatory de novo tumor biopsy (not older than 3 months) sent to central laboratory as formalin-fixed, paraffin-embedded (FFPE) sample for determination of PDL1 status prior to randomization for stratification.
6. Availability of a representative archival FFPE tumor sample (preferable from primary diagnosis)
7. Patient has not progressed on the chosen/planned chemotherapy (PLD or Paclitaxel) in any prior line
8. Patients previously treated with bevacizumab are eligible, with the exclusion of those patients that has suspended bevacizumab for more than 2 subsequent cycles or permanently discontinued bevacizumab during their previous treatment due to toxicity.
9. Females aged ≥ 18 years at signing at time of signing informed consent form
10. Signed written informed consent and ability to comply with the study protocol, in the investigator's judgement
11. Adequate hematological, renal and hepatic function within 28 days prior to first administration of study treatment:

    * Hemoglobin ≥ 9.0 g/dL
    * Absolute neutrophil count (ANC) ≥ 1.5 x 10xE\^9/L
    * Platelet count ≥ 100 x 10xE\^9/L
    * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    * 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 case of liver metastases values must be ≤ 5 x ULN
    * Serum creatinine ≤ 1.5 x institutional ULN
    * 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
    * Urine dipstick for proteinuria \< 2+. If urine dipstick is ≥ 2+, 24-hours urine must demonstrate ≤ 1 g of protein in 24 hours.
12. Patients must have adequately controlled blood pressure (BP), with a systolic BP of ≤ 140 mmHg and diastolic BP of ≤ 90 mmHg for eligibility. Patients must have a BP of ≤ 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to starting study.
13. Estimated life expectancy of at least 3 months
14. ECOG performance status 0 - 1
15. Negative urine or serum pregnancy test within 7 days of study treatment in women of childbearing potential (WOCBP), confirmed prior to treatment on day 1
16. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 5 months after administration of the last dose of atezolizumab/placebo and 6 months after the last dose of bevacizumab, paclitaxel, or PLD, whichever is later.
17. For countries where this will apply to: a patient will be eligible for randomization in this study only, if either affiliated to, or a beneficiary of a social security category.
18. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, that include the completion of patient-reported outcomes questionnaires.

Exclusion Criteria:

1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors)
2. Ovarian tumors of low malignant potential (e.g. borderline tumors)
3. Malignancies other than ovarian cancer within 5 years prior to randomisation, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer)
4. More than three prior systemic anticancer regimens; maintenance therapies (e.g. with bevacizumab, olaparib or niraparib) are not calculated as separate line.
5. Prior systemic anticancer therapy within 28 days before randomization (except bevacizumab: 20 days).
6. Prior radiotherapy to the pelvis or the abdomen.
7. 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 thera-py is permitted).
8. Prior treatment with anti-CD137 or immune checkpoint blockade therapies, anti-PD1, or anti-PD-L1 therapeutic antibodies or anti-CTLA 4
9. Prior randomization in AGO-OVAR 2.29.
10. Treatment with systemic immunostimulatory agents (in-cluding but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day 1.
11. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophos-phamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor \[TNF\] agents) within 2 weeks prior to cycle 1, day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.

    The use of inhaled corticosteroids for chronic obstruc-tive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
12. Patients with a history of allergic reaction to IV contrast requiring steroid pre-treatment should have screening and subsequent tumor assessments performed using magnetic resonance imaging (MRI).
13. Administration of a live, attenuated vaccine within 4 weeks prior to cycle 1, day 1 or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab/placebo. Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccination
14. Major surgery within 4 weeks of starting study treatment or patient who has not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure within 7 days prior to day 1, cycle 1 is permitted.
15. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
16. Current treatment with anti-viral therapy for HBV.
17. History of idiopathic pulmonary fibrosis (including pneumonitis), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evi-dence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) detected on screening chest CT scan is permitted
18. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization
19. History or evidence hemorrhagic disorders within 6 months prior to randomization
20. Patients are excluded if having a history or evidence of thrombosis as follows:

    * Any Grade 4 thrombosis
    * Arterial thrombosis within 6 months prior to ran-domization
    * Grade ≤ 3 venous thrombosis within 3 months prior to randomization Patients with central venous access thrombosis are eligi-ble.
21. 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 sus-pected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of sus-pected spinal cord compression
22. History of autoimmune disease, including but not limited to dermatomyositis, myasthenia gravis, myositis, auto-immune hepatitis, systemic lupus erythematosus, rheu-matoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guil-lain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Except patients with:

    * a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone
    * controlled type 1 diabetes mellitus on a stable insulin regimen

    Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
    * Rash must cover \< 10% of body surface area
    * Disease is well controlled at baseline and requires only low-potency topical corticosteroids
    * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
23. Any prior history of hypertensive crisis (CTCAE grade 4) or hypertensive encephalopathy.
24. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C.

    Patients with past hepatitis B virus (HBV) infection or re-solved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
25. Persistent toxicities (≥ CTCAE grade 2) with the exception of alopecia, caused by previous cancer treatment. Neurotoxicity CTCAE grade 2 is permitted in case the patient is planned for PLD treatment.
26. Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomization, including but not limited to active tuberculosis or hospitalization for complications of infection, bacteremia, or severe pneumonia. Patients receiving prophylactic antibiotics (e.g., to prevent urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
27. Current or recent (within 10 days prior randomization) chronic use of aspirin \> 325 mg/day.
28. Clinically significant (e.g. active) cardiovascular disease, including:

    * Myocardial infarction or unstable angina pectoris within ≤ 6 months of randomization
    * New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF)
    * Poorly controlled cardiac arrhythmia despite medica-tion (patients with rate controlled atrial fibrillation are eligible)
    * Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living \[ADL\] requiring repair or revision)
    * Resting ECG with QTc \>470 msec or family history of long QT syndrome
29. For patients with PLD treatment: Left ventricular ejection fraction defined by ECHO below the institutional lower limit of normal
30. Evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation).
31. Non-healing wound, active ulcer or bone fracture.
32. History of bowel obstruction (including subocclusive disease) related to underlying disease, a history of ab-dominal fistula, GI perforation, or intra-abdominal abscess, or evidence of deep infiltration of the bowel by pelvic examination or on computed tomography, or clinical symptoms of bowel obstruction.
33. Patients with evidence of abdominal free air.
34. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications
35. Known hypersensitivity or allergy to drugs containing Chinese hamster (CHO) ovary cells or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
36. Known hypersensitivity reaction or allergy to drugs chemically related to bevacizumab, paclitaxel, pegylated liposomal doxorubicin, or their excipients that contra-indicates the subject's participation.
37. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. This includes also any psychiatric disorder that prohibits obtaining informed consent.
38. Pregnancy, lactation, or intention to become pregnant during the study or within 5 months after the last dose of atezolizumab/placebo as well as breastfeeding women or intended to breastfeed during the study and up to 6 months after treatment with paclitaxel, bevacizumab and pegylated liposomal doxorubicin (PLD).
39. For France only: Patients deprived of their liberty by judicial or administrative decision and patients under a legal protection measure or unable to express their consent.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomizationrandomization to date of death from any cause assessed up to 40 months
measure: Progression-free survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months
Secondary outcomes:
measure: patient reported outcomes (QLQ and PRO-CTCAE)
timeFrame: every 4 weeks during the first 3 months, then every 12 weeks until PD#1, assessed up to 40 months
measure: Objective Response Rate (ORR)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months
measure: Duration of Response (DOR)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months
measure: Efficacy regarding PD-L1 status
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months
Other outcomes:
measure: Time from randomization to first subsequent therapy (TFST)
timeFrame: at every visit during the trial up to a maximum of 40 months
measure: Time from randomization to second subsequent therapy (TSST)
timeFrame: at every visit during the trial up to a maximum of 40 months
measure: Analysis on LDH levels at baseline
timeFrame: Baseline
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität
city: Edegem
country: Belgium
facility: UZA Edegem
city: Gent
country: Belgium
facility: AZ Sint Lucas
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU Liège Sart Tilman Grivegnée
city: Namur
country: Belgium
facility: CHU UCL Namur Sainte Elisabeth
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Angers
country: France
facility: ICO d'Angers
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besançon
country: France
facility: Hôpital Jean Minjoz
city: Blois
country: France
facility: Blois Hospital (Centre Hospitalier de Blois)
city: Bordeaux
country: France
facility: Clinique TIVOLI-DUCOS
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Challes-les-Eaux
country: France
facility: Médipôle de Savoie
city: Chambray-lès-Tours
country: France
facility: SASU Centre d'Oncologie et Radiothérapie 37
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental Vendée
city: Lille
country: France
facility: Centre Oscar Lambret, Lille
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: ICM Val d'Aurelle
city: Nancy
country: France
facility: ORACLE Centre d'Oncologie de Gentilly
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: Centre Hospitalier Régional d'Orléans
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint Simon
city: Paris
country: France
facility: Institut Curie Site Paris
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Plérin
country: France
facility: Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: IUCT Oncopole - Institut Claudius Regaud
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy
city: Bad Homburg
country: Germany
facility: Hochtaunus-Kliniken
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CVK)
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Essen
country: Germany
facility: Universitätsfrauenklinik Essen
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst
city: Frankfurt
country: Germany
facility: Universitätsfrauenklinik Frankfurt
city: Gütersloh
country: Germany
facility: Klinikum Gütersloh
city: Halle
country: Germany
facility: Universitätsfrauenklinik Halle/Saale
city: Hamburg
country: Germany
facility: Mammazentrum Hamburg am Krankenhaus Jerusalem
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Hildesheim
country: Germany
facility: Praxisgemeinschaft Frauenärzte am Bahnhofsplatz
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken Karlsruhe
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Köln
country: Germany
facility: Universitätsfrauenklinik Köln
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Mannheim
country: Germany
facility: Universitätsfrauenklinik Mannheim
city: Minden
country: Germany
facility: Johannes Wesling Klinikum
city: München
country: Germany
facility: Klinikum der Universität München
city: München
country: Germany
facility: Rotkreuzklinikum München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nordhausen
country: Germany
facility: MVZ Nordhausen
city: Offenburg
country: Germany
facility: Ortenau Klinikum Offenburg-Gengenbach
city: Ravensburg
country: Germany
facility: Onkologie Ravensburg
city: Regensburg
country: Germany
facility: Universitätsfrauenklinik Regensburg
city: Saalfeld
country: Germany
facility: Thüringen Kliniken "Georgius Agricola"
city: Saarbrücken
country: Germany
facility: CTS CaritasKlinikum Saarbrücken
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus
city: Traunstein
country: Germany
facility: Klinikum Traunstein
city: Tübingen
country: Germany
facility: Universitätsfrauenklinik Tübingen
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
city: Wiesbaden
country: Germany
facility: Helios Dr. Horst Schmidt Kliniken
city: Witten
country: Germany
facility: Marien-Hospital
city: Wolfsburg
country: Germany
facility: AMO MVZ Wolfsburg
city: Kaunas
country: Lithuania
facility: Vilniaus universiteto ligoninė Santaros klinikos
city: Vilnius
country: Lithuania
facility: Nacionalinis vėžio institutas
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia (ICO) d'Hospitalet
city: Barcelona
country: Spain
facility: Vall d'Hebron Instituto de Oncología (VHIO)
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Girona
country: Spain
facility: Institut Català d'Oncologia (ICO) de Girona
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez
city: La Paz
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra (CUN)
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Llàtzer
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra (CUN)
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología (IVO)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Malmö
country: Sweden
facility: Skåne University Hospital
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Frauenfeld
country: Switzerland
facility: Kantonsspital Frauenfeld
city: Luzern
country: Switzerland
facility: Kantonsspital Luzern
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
Study officials:
affiliation: Kliniken Essen-Mitte, Germany
name: Philipp Harter, MD, PhD
role: STUDY_CHAIR
References:
citation: Harter P, Pautier P, Van Nieuwenhuysen E, Reuss A, Redondo A, Lindemann K, Kurzeder C, Petru E, Heitz F, Sehouli J, Degregorio N, Wimberger P, Burges A, Cron N, Ledermann J, Lorusso D, Paoletti X, Marme F. Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer - a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34). Int J Gynecol Cancer. 2020 Dec;30(12):1997-2001. doi: 10.1136/ijgc-2020-001572. Epub 2020 Jun 30.