Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer

Stage IV Breast Cancer AJCC v6 and v7 Clinical Trial

Official title:

A Randomized, Double-Blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03199885
• Other study ID #: NCI-2017-01119
• Secondary ID: NCI-2017-01119NR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 5, 2019
• Est. completion date: May 15, 2025

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body (metastatic). Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may interfere with the ability of cancer cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells. *NOTE: This study has a central confirmation step. The purpose of this step is to confirm by central testing that the patient's tumor has specific receptors. If the patient meets all the study requirements, the patient will join the study and begin therapy for breast cancer while the tumor is being tested.

Description:

PRIMARY OBJECTIVE: I. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the progression-free survival (PFS), assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, relative to the addition of a placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) in patients with newly documented HER2-positive measurable metastatic breast cancer. SECONDARY OBJECTIVES: I. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the overall survival (OS) relative to the addition of placebo to a regimen of pertuzumab and trastuzumab, combined with a taxane (paclitaxel or docetaxel). II. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the overall objective response (OR) in the cohort of patients randomized 6 months or more prior to study accrual closure assessed by investigator using RECIST 1.1 criteria, relative to the addition of placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). III. To determine the immune-related toxicity profile of the two treatment regimens. IV. To determine the cardiac safety profile of the two treatment regimens. EXPLORATORY OBJECTIVES: I. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will decrease the incidence of subsequent brain metastases in patients without known brain metastases at study entry relative to the addition of a placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). II. To determine the utility of PD-L1 immunohistochemistry (IHC) staining as a predictive and prognostic biomarker associated with clinical response, as assessed by investigator using RECIST 1.1 criteria, to atezolizumab in combination with trastuzumab and pertuzumab combined with a taxane (paclitaxel or docetaxel). III. To identify potential biomarkers that can predict benefit from the addition of atezolizumab in patients with newly documented HER2-positive measurable metastatic breast cancer treated with a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). IV. To explore the toxicity profile of the two treatment regimens using patient-reported symptomatic adverse events in addition to standard adverse event reports. V. To determine the feasibility and added value of frequent assessment of toxicity using Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) with electronic(e)PRO reporting. VI. To explore whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will contribute to increased patient-reported fatigue in comparison to the addition of placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). OUTLINE: STEP 1: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo a biopsy at baseline. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or bone scan at baseline. STEP 2: Patients are randomized to 1 of 2 arms. ARM I: Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22 of each cycle, trastuzumab IV over 30-90 minutes on days 1 and 22 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 of each cycle or docetaxel IV over 60 minutes on days 1 and 22 of each cycle. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. ARM II: Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. After completion of study treatment, patients are followed up at 30 days and every 3 months for 3 years and then every 6 months for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 190
• Est. completion date: May 15, 2025
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
• The trial is open to female and male patients
• Patients must be >= 18 years old
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease outside the central nervous system (CNS)

confirmed as described below; eligible patients include those with either:

• De novo metastatic disease presenting without prior history of HER2-positive

breast cancer:

• Diagnosis should have been made from a biopsy of a metastatic disease site, but biopsy from the breast primary or involved regional lymph nodes is acceptable if biopsy of the metastatic sites was thought to carry excessive risk for the patient
• Locally recurrent or metastatic disease following prior therapy for early breast

cancer:

• Diagnosis must have been made from the biopsy of the locally recurrent or metastatic disease
• There must be an interval of >= 6 months between completion of neoadjuvant/adjuvant HER2-targeted therapy and documentation of locally recurrent or metastatic HER2-positive disease by biopsy
• Patients must have measurable disease based on RECIST 1.1, as determined by the site, which has not been irradiated to be eligible
• Patients with brain metastases are eligible if they meet ALL the following criteria:
• Four or fewer metastatic sites to CNS
• Largest unexcised tumor does not exceed 3 cm
• No metastases to brain stem, midbrain, pons, medulla or the optic nerves and chiasm
• Must have measurable disease outside the CNS, based on RECIST 1.1, as determined by the site, which has not been irradiated
• If patient presented with symptoms from CNS metastases, the symptoms must have resolved with initiation of steroids and initial local therapy (surgery, radiation therapy, or both)
• Must have been evaluated by Medical Oncologist and plan is to administer trastuzumab, pertuzumab, and a taxane as first-line systemic therapy
• May have received administration of trastuzumab OR lapatinib concurrently with radiation therapy for brain metastases. Toxicities related to lapatinib if administered, should be =< grade 1 per the CTCAE v5.0, and the lapatinib must have been completed at least 2 weeks prior to study entry
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No neurosurgical resection or brain biopsy within 10 days prior to study entry
• After study entry and before randomization, send tissue for central HER2 confirmation; a tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been determined to be HER2-positive based on local testing according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (Wolff 2018); HER2 status should initially be assessed using an Food and Drug Administration (FDA)-cleared IHC assay; positive is defined as IHC 3+ staining intensity; if HER2 IHC results are equivocal (2+), then HER2 status will be determined using a FDA-cleared HER2 in situ hybridization (ISH) test according to ASCO/CAP guidelines; Note: Once HER2-positive is confirmed on central testing, patients will be randomized to atezolizumab/placebo; randomization within 14 days from study entry will ensure that the Pharmaceutical Management Branch (PMB)-supplied agents will be received at the site for treatment on day 22 of cycle 1
• The tumor specimen obtained at the time of diagnosis used for HER2 testing must also have central testing for PD-L1 status; patients will be eligible irrespective of PD-L1 testing result including PD-L1 indeterminant
• The tumor specimen obtained at the time of diagnosis used for HER2 and PD-L1 testing should also have central testing for estrogen receptor (ER) and progesterone receptor (PgR) according to current ASCO/CAP guideline recommendations for hormone receptor testing; patients with < 1% ER and PgR staining by IHC will be classified as negative; if enough material for central confirmation of ER and PgR is unavailable, local testing results for ER and PgR may be used for eligibility
• Localized palliative radiation therapy to sites of non-measurable disease is allowed for symptom management and may begin prior to study entry and continue following study entry while receiving study therapy
• Patients must have imaging of the chest/abdomen/pelvis, preferably with a CT scan, and a bone scan within 5 weeks prior to study entry; (NOTE: if a patient is unable to receive CT contrast, a MRI of the abdomen/pelvis and non-contrast chest CT should be performed; positron emission tomography/computed tomography [PET/CT] is not an acceptable alternative)
• MRI of the brain (or contrast CT scan of the brain if patients are unable to undergo MRI) must be obtained in patients with symptoms suggesting possible central nervous system (CNS) metastatic disease; neuroimaging is recommended but not required in asymptomatic patients
• Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 14 days prior to study entry)
• Platelet count must be >= 100,000/mm^3 (within 14 days prior to study entry)
• Hemoglobin must be >= 8 g/dL (within 14 days prior to study entry)
• Total bilirubin must be =< 1.5 x upper limit of normal (ULN) for the lab or direct bilirubin =< ULN for patients with bilirubin levels > 1.5 x ULN (within 14 days prior to study entry)
• Aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) must be =< 2.5 x ULN for the lab or =< 5 x ULN for patients with liver metastases (within 14 days prior to study entry)
• Serum creatinine =< 1.5 x ULN or measured or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab (within 14 days prior to study entry)
• Patients not receiving anti-coagulant therapy must have prothrombin time (PT) and international normalized ratio (INR) =< 1.5 x ULN within 14 days prior to study entry; for laboratories that do not report an ULN for the INR assay, use =< 1.5 as the value for the ULN; patients receiving anti-coagulants should have a baseline INR assessed, but the value does not affect eligibility
• A serum thyroid-stimulating hormone (TSH) and AM (preferably in morning) cortisol must be obtained within 14 days prior to study entry to obtain a baseline value; patients with abnormal TSH or AM cortisol baseline levels should be further evaluated and managed per institutional standards; asymptomatic patients who require initiation or adjustment of medication or are followed without initiating treatment based on endocrinologist's recommendations are eligible
• Left ventricular ejection fraction (LVEF) assessment must be performed within 6 weeks prior to study entry; (LVEF assessment performed by echocardiogram is preferred; however, multigated acquisition scan (MUGA) scan may be substituted based on institutional preferences); the LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal
• Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab/placebo and 7 months after the last dose of trastuzumab and pertuzumab; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of study entry are eligible for this trial

Exclusion Criteria:

• Patients with brain metastases are excluded if they meet ANY of the following

criteria:

• Symptoms from brain metastases have not resolved prior to study entry
• Five or more clearly identified foci of metastases to the brain
• Largest unexcised tumor exceeds 3 cm
• Spinal cord metastases
• Medical Oncologist plans to employ HER2-directed tyrosine kinase inhibitor as component of systemic therapy
• Metastatic disease limited to CNS
• Leptomeningeal carcinomatosis
• History of systemic anti-cancer therapy (e.g., chemotherapy, targeted therapy) for metastatic breast cancer (MBC) except as described in inclusion criteria
• History of exposure to cumulative doses of doxorubicin greater than 360 mg per square meter of body-surface area or its equivalent
• Prior treatment with mTOR inhibitors or CDK 4/6 inhibitors in combination with endocrine therapy for treatment of metastatic disease
• Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry
• Uncontrolled hypertension defined as sustained systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg; (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
• History of asymptomatic LVEF decline to < 40% during or after prior HER2-targeted therapy even if the current LVEF is >= 50%
• Cardiac disease (history of and/or active disease) that would preclude the use of the

drugs included in the treatment regimens; this includes but is not confined to:

• Active cardiac disease
• Angina pectoris that requires the current use of anti-anginal medication;
• Ventricular arrhythmias except for benign premature ventricular contractions;
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
• Conduction abnormality requiring a pacemaker;
• Valvular disease with documented compromise in cardiac function; or
• Symptomatic pericarditis
• History of cardiac disease
• Prior myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function;
• History of documented congestive heart failure (CHF) defined as symptomatic heart failure with an LVEF < 40%; or
• Documented cardiomyopathy
• Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2, per the CTCAE v 5.0
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to pertuzumab or trastuzumab or to any of its excipients, as well as any chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or other recombinant antibodies
• Known allergy or hypersensitivity to the components of the atezolizumab formulation or to any of the study drugs or excipients, (e.g., Cremophor EL, polysorbate 80)
• History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would

be excluded) are permitted provided that they meet the following conditions:

• Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
• Rash must cover less than 10% of body surface area (BSA)
• Disease is well controlled at baseline and only requiring low-potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
• No acute exacerbations of underlying conditions within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
• Treatment with systemic immunomodulatory medications (including but not limited to interferons, IL-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to study entry
• Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis [anti-TNF] factor agents) within 14 days prior to study entry or anticipation of need for systemic immunosuppressive medications during the study; Note: Intranasal and inhaled corticosteroids or systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or an equivalent corticosteroid are allowed
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to study entry
• Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test at screening; patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study if active HBV infection is ruled out on the basis of HBV deoxyribonucleic acid (DNA) viral load per local guidelines
• Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV ribonucleic acid (RNA)
• Patients with clinically active tuberculosis
• Severe infection within 4 weeks prior to study entry, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Prior allogeneic stem cell or solid organ transplantation
• Symptomatic peripheral ischemia
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis or >= grade 1 pulmonary fibrosis, per the CTCAE v5.0, on screening chest CT scan
• Administration of a live, attenuated vaccine within 4 weeks prior to study entry or anticipation that such vaccine will be required during the study
• Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to study entry, during treatment or within 5 months following the last dose of atezolizumab/placebo
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results
• Pregnancy or lactation at the time of study entry or intention to become pregnant during the study; (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 3 days prior to study entry)
• Use of any investigational product within 4 weeks prior to study entry

Related Conditions & MeSH terms

• Adenocarcinoma
• Breast Neoplasms
• Carcinoma
• Metastatic Breast Adenocarcinoma
• Recurrence
• Stage III Breast Cancer AJCC v7
• Stage IV Breast Cancer AJCC v6 and v7
• Unresectable Breast Carcinoma

Intervention

Drug:
• Atezolizumab
Given IV

Procedure:
• Biopsy
Undergo biopsy
• Bone Scan
Undergo bone scan
• Computed Tomography
Undergo CT scan

Drug:
• Docetaxel
Given IV

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Drug:
• Paclitaxel
Given IV

Biological:
• Pertuzumab
Given IV

Other:
• Placebo Administration
Given IV
• Quality-of-Life Assessment
Ancillary studies

Biological:
• Trastuzumab
Given IV

Locations

Country	Name	City	State
Canada	William Osler Health System-Brampton Civic Hospital	Brampton	Ontario
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec
Canada	London Regional Cancer Program	London	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Algoma District Cancer Program Sault Area Hospital	Sault Ste Marie	Ontario
Canada	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA-Vancouver Island Cancer Centre	Victoria	British Columbia
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Phoebe Putney Memorial Hospital	Albany	Georgia
United States	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Randolph Hospital	Asheboro	North Carolina
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Messino Cancer Centers	Asheville	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	University Cancer and Blood Center LLC	Athens	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Hematology Oncology Associates of Central New York-Auburn	Auburn	New York
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Augusta Oncology Associates PC-D'Antignac	Augusta	Georgia
United States	Augusta Oncology Associates PC-Wheeler	Augusta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	GenesisCare USA - Aventura FP	Aventura	Florida
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Kaiser Permanente-Woodlawn Medical Center	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Our Lady of the Lake Medical Oncology	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physician Group	Baton Rouge	Louisiana
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Waldo County General Hospital	Belfast	Maine
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Beverly Hospital	Beverly	Massachusetts
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	GenesisCare USA - Boca Ration FP06	Boca Raton	Florida
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	United Hospital Center	Bridgeport	West Virginia
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Wellmont Medical Associates-Bristol	Bristol	Virginia
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Crozer-Keystone Regional Cancer Center at Broomall	Broomall	Pennsylvania
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Kaiser Permanente-Burke Medical Center	Burke	Virginia
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	AdventHealth Celebration	Celebration	Florida
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	AdventHealth Infusion Center Haywood	Clyde	North Carolina
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Main Line Health Center-Collegeville	Collegeville	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Cookeville Regional Medical Center	Cookeville	Tennessee
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	UC Irvine Health Cancer Center-Newport	Costa Mesa	California
United States	Northshore Oncology Associates-Covington	Covington	Louisiana
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Northwest Cancer Center - Main Campus	Crown Point	Indiana
United States	AMG Crystal Lake - Oncology	Crystal Lake	Illinois
United States	Danbury Hospital	Danbury	Connecticut
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Cancer Center of Colorado at Sloan's Lake	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Kaiser Permanente Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Northside Hospital - Duluth	Duluth	Georgia
United States	Northwest Oncology LLC	Dyer	Indiana
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Saint Vincent Hospital	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Exeter Hospital	Exeter	New Hampshire
United States	Main Line Health Center-Exton	Exton	Pennsylvania
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	FMH James M Stockman Cancer Institute	Frederick	Maryland
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Washington Hospital	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Kaiser Permanente-Gaithersburg Medical Center	Gaithersburg	Maryland
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Levine Cancer Institute-Gaston	Gastonia	North Carolina
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Crozer Regional Cancer Center at Brinton Lake	Glen Mills	Pennsylvania
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Smilow Cancer Hospital Care Center at Greenwich	Greenwich	Connecticut
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut
United States	Gulfport Memorial Hospital	Gulfport	Mississippi
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	HaysMed	Hays	Kansas
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	South Carolina Cancer Specialists PC	Hilton Head Island	South Carolina
United States	Northwest Cancer Center - Hobart	Hobart	Indiana
United States	Saint Mary Medical Center	Hobart	Indiana
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Oncology Center of The South Incorporated	Houma	Louisiana
United States	Houston Methodist Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Saint Catherine Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	Vidant Oncology-Kenansville	Kenansville	North Carolina
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kaiser Permanente - Kensington Medical Center	Kensington	Maryland
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee
United States	ECU Health Oncology Kinston	Kinston	North Carolina
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Thompson Cancer Survival Center - West	Knoxville	Tennessee
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Ann B Barshinger Cancer Institute	Lancaster	Pennsylvania
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	Mid-Michigan Physicians-Lansing	Lansing	Michigan
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Kaiser Permanente - Largo Medical Center	Largo	Maryland
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Northside Hospital - Gwinnett	Lawrenceville	Georgia
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Thompson Oncology Group-Lenoir City	Lenoir City	Tennessee
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	Cancer Partners of Nebraska	Lincoln	Nebraska
United States	Cancer Partners of Nebraska - Pine Lake	Lincoln	Nebraska
United States	Atrium Health Lincoln/LCI-Lincolnton	Lincolnton	North Carolina
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Thompson Oncology Group-Maryville	Maryville	Tennessee
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Kaiser Permanente Tysons Corner Medical Center	McLean	Virginia
United States	Redeemer Health	Meadowbrook	Pennsylvania
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Summa Health Medina Medical Center	Medina	Ohio
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Memorial Medical Center	Modesto	California
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	The Community Hospital	Munster	Indiana
United States	Women's Diagnostic Center - Munster	Munster	Indiana
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	ThedaCare Regional Medical Center - Neenah	Neenah	Wisconsin
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai Union Square	New York	New York
United States	Mount Sinai West	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Piedmont Newnan Hospital	Newnan	Georgia
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Thompson Oncology Group-Oak Ridge	Oak Ridge	Tennessee
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	Integris Cancer Institute of Oklahoma	Oklahoma City	Oklahoma
United States	Integris Southwest Medical Center	Oklahoma City	Oklahoma
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Kaiser Permanente-Ontario	Ontario	California
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Desert Regional Medical Center	Palm Springs	California
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Eastern Regional Medical Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Banner-University Medical Center Phoenix	Phoenix	Arizona
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Women and Infants Hospital	Providence	Rhode Island
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Vidant Oncology-Richlands	Richlands	North Carolina
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Kaiser Permanente-Richmond	Richmond	California
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Neurosurgeons of New Jersey-Ridgewood	Ridgewood	New Jersey
United States	Valley Health System Ridgewood Campus	Ridgewood	New Jersey
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina
United States	UW Health Carbone Cancer Center Rockford	Rockford	Illinois
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Nash UNC HealthCare	Rocky Mount	North Carolina
United States	Kaiser Permanente-Roseville	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Community Medical Center	Scranton	Pennsylvania
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Suburban Hematology Oncology Associates - Snellville	Snellville	Georgia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	City of Hope South Pasadena	South Pasadena	California
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Piedmont Henry Hospital	Stockbridge	Georgia
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Banner Boswell Medical Center	Sun City	Arizona
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Hematology Oncology Associates of Central New York-Onondaga Hill	Syracuse	New York
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	City of Hope South Bay	Torrance	California
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	UM Saint Joseph Medical Center	Towson	Maryland
United States	Munson Medical Center	Traverse City	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Cancer Treatment Centers of America	Tulsa	Oklahoma
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	City of Hope Upland	Upland	California
United States	Crozer-Chester Medical Center	Upland	Pennsylvania
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Northwest Cancer Center - Valparaiso	Valparaiso	Indiana
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Kaiser Permanente-Capitol Hill Medical Center	Washington	District of Columbia
United States	Marion L Shepard Cancer Center - ECU Health Beaufort Hospital	Washington	North Carolina
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Valley Medical Group - Wayne Multispecialty Practice	Wayne	New Jersey
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Good Samaritan University Hospital	West Islip	New York
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	University of Michigan Health - West	Wyoming	Michigan
United States	UPMC Memorial	York	Pennsylvania
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Will be determined using the current Response Evaluation Criteria in Solid Tumors 1.1 criteria. Analysis will be based on the intent to treat population. The stratified log-rank test will be used to compare the progression free survival between the two treatment arms with the following stratification factors: prior neoadjuvant or adjuvant therapy with trastuzumab (no; yes), estrogen receptor status (positive; negative), disease sites (any visceral without brain metastasis; non-visceral only without brain metastasis; brain metastasis), and choice of taxane (paclitaxel; docetaxel). The Kaplan-Meier estimates will be calculated by treatment arms. Stratified Cox proportional hazards models to estimate the hazard ratio.	The time from randomization to the first documented progressive disease every 6 months, assessed up to 8 years
Secondary	Overall survival	Analysis will be based on the intent to treat population. The stratification factors are the same as what are used in the stratified log-rank test for the primary analysis on progression free survival. The Kaplan-Meier estimates will be calculated by treatment arms. Stratified Cox proportional hazards models to estimate the hazard ratio.	The time from randomization to death from any cause every 6 months, assessed up to 8 years
Secondary	Overall objective response	Defined as complete response or partial response. Will be determined using Response Evaluation Criteria in Solid Tumors 1.1 criteria. The stratified Cochran-Mantel-Haenszel test will be used to compare the object response between the treatment arms.	Every 6 months up to 8 years
Secondary	Frequency of adverse events, including late immune-related toxicities	Will be categorized using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. Comparisons of the adverse events between the two treatment arms will be done by the Fisher's exact test.	Every 6 months up to 8 years