Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy.
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT03161353
- Lead Sponsor
- MedSIR
- Brief Summary
The study assess the early metabolic effects of neoadjuvant treatment with trastuzumab and pertuzumab (± endocrine therapy) on the primary tumor and axillary lymph nodes and their predictive value for pathologic complete response (pCR) in the breast and axilla.
And also assess 3-year invasive disease-free survival (iDFS) in patients with HER2-positive (HER: human epidermal receptor) breast cancer treated with neoadjuvant trastuzumab and pertuzumab (± endocrine therapy) using a FDG-PET response-adapted strategy.
- Detailed Description
Investigational Medicinal Products (IMPs) will be trastuzumab and pertuzumab, carboplatin, and docetaxel, as well as all endocrine therapy drugs to be administered according to HR status (hormone receptor). For cohort C, trastuzumab SC (subcutaneous) and pertuzumab IV will be IMPs until a maximum of 18 cycles.
Patients will be randomly assigned in a 1:4 ratio, with a randomization stratified by HR status to receive trastuzumab and pertuzumab with docetaxel and carboplatin (cohort A) or trastuzumab and pertuzumab ± endocrine therapy according to HR status (cohort B).
A F-FDG PET/CT will be performed at baseline (total body) and after 2 cycles of neoadjuvant therapy. Central review of F-FDG PET/CT will be mandatory. Patients allocated into cohort A will continue with the same treatment for a total of six cycles regardless of 18F-FDG PET/CT results. Patients enrolled into cohort B showing at least 40% reduction of the SUVmax of F-FDG PET/CT respect to baseline (PET responders) will continue with the same treatment for a total of 8 cycles. PET-non responders patients will also receive neoadjuvant chemotherapy based on six cycles of docetaxel and carboplatin concurrently with trastuzumab and pertuzumab for all cycles.
Following surgery, cohort B/PET responders patients who do not achieve a pCR will additionally receive six cycles of docetaxel and carboplatin concurrently with trastuzumab and pertuzumab for all cycles. Moreover, all patients from cohorts A/B must complete 18 cycles of trastuzumab and pertuzumab, along with adjuvant endocrine therapy and radiotherapy according to HR status (hormone receptor) and institutional practices, respectively.
An additional exploratory cohort (cohort C) will include patients with evidence of subclinic M1 at baseline 18F-FDG PET/CT, but not previously detected by routine clinical assessment. These patients will receive trastuzumab and pertuzumab with docetaxel and carboplatin for a total of six cycles. After first six cycles, these patients will receive trastuzumab and pertuzumab ± endocrine.therapy according to HR status for at least 12 additional cycles after surgery (only if surgery is performed). According to institutional practices, it will be allowed to continue treatment with trastuzumab and pertuzumab, along endocrine therapy on the basis of HR status, as maintenance therapy until disease progression or unacceptable toxicity.
A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study" : Hospital General de Valencia, Hospital Clínico Universitario de Valencia, IVO, Hospital La Fe and Hospital Arnau de Vilanova.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 377
- Written informed consent prior to beginning specific protocol procedures.
- Female or male patients ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Histologically proven invasive breast cancer.
- Operable breast cancer (cT1-3 and/or cN0-2 tumors) (breast cancer TNM classification)
- Tumor size larger than or equal to 1.5 centimeter (cm) in diameter by magnetic resonance imaging (MRI) or ultrasound with a significant 18F-FDG uptake defined as maximum standarized uptake value (SUVmax: maximum standarized uptake value) ≥1.5 x SUVmean (mean standarized uptake value) liver + 2 SD (standard deviation.
Multicentric/multifocal tumors will be allowed only if:
- Histological confirmation of at least two lesions.
- All tumors must be HER2-positive.
- Largest lesion must be larger than or equal to 1.5 cm in diameter by MRI or ultrasound.
7)Centrally confirmed HER2-positive disease according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria.
8)Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry.
Patient has adequate bone marrow, liver, and renal function:
9)Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L).
10)Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (except for Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 times ULN.
11)Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
12)Patient must be accessible for treatment and follow-up.
- Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer.
- cT4 and/or cN3 tumors (TNM breast cancer classification)
- Bilateral breast cancer.
- Evidence of metastatic disease by routine clinical assessment chest x-ray, liver ultrasound, and bone scan; or computed tomography (CT) scan of thorax and abdomen and bone scan, except patients with subclinic M1 (metastases) at baseline only according to 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) that will be allowed to be included into cohort C.
- Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
- History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma.
- Left ventricular ejection fraction (LVEF) below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO).
- Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment.
- Clinically significant cardiovascular disease [stroke, unstable angina pectoris, or documented myocardial infarction within six months prior to study entry; history of documented congestive heart failure (CHF) (New York Heart Association II-III-IV); symptomatic pericarditis; documented cardiomyopathy; ventricular arrythmias with the exception of benign premature ventricular contractions; conduction abnormality requiring a pacemaker; other arrhythmias not controlled with medication].
- Active uncontrolled infection at the time of enrollment.
- Current known infection with HIV, hepatitis B virus, or hepatitis C virus.
- Patients with pulmonary disease requiring continuous oxygen therapy.
- Previous history of bleeding diathesis.
- Patient is currently receiving anti-coagulant therapy, chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed).
- Major surgical procedure or significant traumatic injury within 14 days prior to randomization or anticipation of need for major surgery within the course of the study treatment.
- Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the investigator´s judgment, contraindicate her participation in the clinical study.
- Concurrent participation in other clinical trial, except other translational studies.
- History of receiving any investigational treatment within 28 days prior to randomization.
- Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.
LINGain sub-study: The LINGAIN project intends to include a total of 126 blood samples from PHERGain trial, as follows:
105 from patients treated with trastuzumab and pertuzumab ± endocrine therapy (according to HR status); 21 from patients treated with trastuzumab and pertuzumab + carboplatin and docetaxel.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A Perjeta Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort A Herceptin Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort B Perjeta Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. * PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. * PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort B Herceptin Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. * PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. * PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort C Perjeta cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery. Cohort C Herceptin cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery. Cohort A Docetaxel Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort A Carboplatin Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort A Letrozole Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort A Tamoxifen Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort B Docetaxel Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. * PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. * PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort B Carboplatin Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. * PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. * PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort B Letrozole Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. * PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. * PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort B Tamoxifen Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. * PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. * PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study". Cohort C Carboplatin cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery. Cohort C Docetaxel cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery. Cohort C Tamoxifen cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery. Cohort C Letrozole cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery.
- Primary Outcome Measures
Name Time Method Evaluate the rate of pCR After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months) evaluate the rate of pCR as defined by the absence of invasive disease in the breast and axilla (ypT0/isN0) at the time of surgery achieved with the combination of trastuzumab and pertuzumab (± endocrine therapy) as exclusive neoadjuvant treatment in PET responders patients (cohort B/PET responders) \[PET/CT positive predictive value (PPV) for a pCR among patients who are PET responders\].
3-year iDFS rate After 3 years (36 months) time from the first date of no disease (i.e., date of surgery) to invasive recurrence, new invasive disease, or death by any cause. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria. The primary analysis will be to estimate 3-year iDFS rate in cohort B.
- Secondary Outcome Measures
Name Time Method Rate of breast conserving surgery After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months) Rate of breast conserving surgery (cohort A; cohort B; cohorts A/B by PET responder status).
18F-FDG PET/CT response rate (18F-FDG: 18F-fluorodeoxyglucose) After cycle 2 (each cycle 21 days- After 42 days approximately) 18F-FDG PET/CT response rate (according to the adapted EORTC criteria) (cohort A; cohort B).
pCR rates in the breast and axilla (ypTO/isN0) After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months) pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohorts A/B by PET responder status).
pCR rates in the breast (ypT0/is) After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months) pCR rates in the breast (ypT0/is) (cohort A; cohort B; cohorts A/B by PET responder status).
RCB score (residual cancer burden) After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months) RCB score (cohort A; cohort B; cohorts A/B by PET responder status).
pCR rates in the breast and axilla After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months) pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohorts A/B by PET responder status; HR status, HER2 status and tumor stage).
Optimal 18F-FDG PET/CT cut-off for pCR After cycle 2 (each cycle 21 days-After 42 days approximately) Optimal 18F-FDG PET/CT cut-off for pCR (cohort A; cohort B).
Other 18FDG PET quantification parameters After cycle 2 (each cycle 21 days- After 42 days approximately) Other 18F-FDG PET quantification parameters beside SUVmax for pCR (cohort A; cohort B). We will consider alternative measures to SUVmax in order to improve the ability to predict pCR; The best predictive parameter will be selected by means of logistic regressions models. For all tests, we will use two sided p-values with alpha ≤ 0.05 level of significance. The p-values emerging from these analyses will not be interpreted in a confirmative sense; they will be considered of descriptive nature only.
MRI response rate After two cycles of neoadjuvant therapy, and prior to surgery (each cycle 21 days) MRI response rate (according to the RECIST criteria version 1.1) (cohort A; cohort B; cohorts A/B by PET responder status).
Health-related quality of life Baseline, cycle 3 (after 63 days approximately), before surgery and end of study through study completion (after cycle 18- after 12 months approximately) Health-related quality of life (EORTC QLQ-C30- quality of life questionnaire and EORTC QLQ-BR23 quality of life questionnaires) (cohort A; cohort B; cohort C; cohorts A/B by PET responder status). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/quality of life scale, and six single itemsThe QLQ-BR23 (quality of life questionnaire) breast cancer module is meant for use among patients varying in disease stage and treatment modality.The scoring approach for the QLQ-BR23 (quality of life questionnaire) is identical in principle to that for the function and symptom scales/single items of the QLQ-C30.
3, 5, and 7-year iDFS After 3, 5 and 7 years (After 36, 60 and 80 months) 3, 5, and 7-year iDFS (cohort A; cohort B \[with the exception of 3-year iDFS\]; cohorts A/B by PET responder status, HR status, and HER2 status).
3,5 and 7-year DDFS (DDFS:Distant disease-free survival) After 3, 5 and 7 years (After 36, 60 and 80 months) 3, 5, and 7-year DDFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status).
3, 5 and 7-year DFS (DFS:Disease-free survival) After 3, 5 and 7 years (After 36, 60 and 80 months) 3, 5, and 7-year DFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status).
3, 5 and 7-year (OS: overall survival) After 3, 5 and 7 years (After 36, 60 and 80 months) 3, 5, and 7-year OS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status)
To assess 3, 5, and 7-year adapted iDFS, DDFS, and DFS After 3, 5 and 7 years (After 36, 60 and 80 months) To assess 3, 5, and 7-year adapted iDFS, DDFS, and DFS on patients with subclinical M1 at baseline by 18F-FDG PET/CT - cohort C.
PFS (cohort C) (PFS: Progression-free survival) Until progression or death, assessed up to approximately 84 months PFS (patients with subclinical M1 at baseline by 18F-FDG PET/CT - cohort C).
Adverse events Until progression or death, assessed up to approximately 84 months Adverse events, grade 3-4 adverse events, related adverse events, serious adverse events, related serious adverse events, and adverse events leading to discontinuation (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status).
3, 5, and 7-year EFS After 3, 5 and 7 years (After 36, 60 and 80 months) 3, 5, and 7-year EFS (cohort A; cohort B).
Trial Locations
- Locations (55)
Hospital Georges Pompidou
🇫🇷Paris, France
Istituto Europeo di Oncologia
🇮🇹Milan, Italy
Hospital Senhora da Oliveira
🇵🇹Guimarães, Portugal
Hospital Fernando Fonseca
🇵🇹Lisboa, Portugal
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario de Burgos
🇪🇸Burgos, Spain
Hospital Reina Sofía
🇪🇸Cordoba, Spain
Ospedale San Gerardo
🇮🇹Monza, Italy
Ospedale Guglielmo de Saliceto
🇮🇹Piacenza, Italy
Hospital Provincial de Castellón
🇪🇸Castello, Castelló, Spain
ICO l'Hospitalet
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Institute de Cancerologie de Laurraine
🇫🇷Nancy, France
Hospital Clínic Universitari de Valencia
🇪🇸Valencia, Spain
Hospital General Universitari de Valencia
🇪🇸Valencia, Spain
Hospital La Paz
🇪🇸Madrid, Spain
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
ICO Badalona
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario A Coruña
🇪🇸A Coruna, Spain
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Istituto Ospedalieri di Cremona
🇮🇹Cremona, Italy
Barts Cancer Institute
🇬🇧London, United Kingdom
Institut Claudius Régaud
🇫🇷Toulouse, France
Hospital Vall D'Hebrón
🇪🇸Barcelona, Spain
Hospital Arnau de Vilanova
🇪🇸Valencia, Spain
Hospital Dr Peset
🇪🇸Valencia, Spain
National center for tumor disease NCT
🇩🇪Heidelberg, Germany
Clinical of Nuclear Medicine Technical University Munich
🇩🇪Munich, Germany
Institute Jules Bordet
🇧🇪Bruxelles, Belgium
Hopital Tenon
🇫🇷Paris, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Kliniken Essen Mitte
🇩🇪Essen, Germany
Städtisches Klinikum "St. Georg" Leipzig
🇩🇪Leipzig, Germany
Ospedale Antonio Perrino
🇮🇹Brindisi, Italy
Ospedale Maggiore Bologna
🇮🇹Bologna, Italy
Ospedale Mantova
🇮🇹Mantova, Italy
Hospital San Joan de Reus
🇪🇸Reus, Tarragona, Spain
CHUS Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Hospital Lozano Blesa
🇪🇸Zaragoza, Spain
Hospital Universitario Miquel Servet
🇪🇸Zaragoza, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
CLCC d'Auvergne. Centre Jean Perrin.
🇫🇷Clermont-Ferrand, France
Groupe Hospitalier Diaconesses
🇫🇷Paris, France
Hämatologisch-Onkologische Schwerpunktpraxis
🇩🇪Munchen, Germany
Hospital Clínic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Klinikum der Med. Fakultät Halle
🇩🇪Halle, Germany
ICO Girona
🇪🇸Girona, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Málaga, Spain
Hospital Beatriz Angelo
🇵🇹Lisboa, Portugal
Hospital do Santo Antonio
🇵🇹Oporto, Portugal
Hospital da Luz
🇵🇹Lisboa, Portugal
Centro Hospitalar Sao Joao
🇵🇹Oporto, Portugal
Centro Hospitalaer de Tras-os-Montes e Alto Douro
🇵🇹Vila Real, Portugal
Hospital de Jaén
🇪🇸Jaen, Jaén, Spain