Localized ER+ breast cancer MedDRA version: 20.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10070577 Term: Oestrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 100
Conditions
Sponsors
European Organisation for research and treatment of Cancer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Women or men with stage II or stage III, early invasive breast cancer according to the UICC 8th edition for TNM classification - Histologically confirmed ER+ (at least 10 % of cells staining positive for ER), HER-2 negative, early invasive breast cancer based on results of local pathology. Testing may be performed on diagnostic core biopsy or resection specimen. - In patients with multicentric, multifocal and/or bilateral breast cancer, all histopathologically examined invasive tumors must meet pathologic criteria regarding ER and HER2-status described above. - Adjuvant chemotherapy indicated and feasible according to treating physician and patient, based on standard clinicopathological parameters (tumor size, lymph node involvement, general health status, proliferation marker, patient wish) and gene expression profile if available. - Adjuvant chemotherapy with both anthracycline and taxanes (in combination or in sequence) considered not indicated or not feasible according to treating physician. - Age =70 years - WHO Performance status 0-2 - Completed G8 geriatric assessment within 3 weeks of randomization. - Participation in translational research is mandatory and therefore patient must consent for it. Patient should allow sequential sampling of blood during the course of the trial - Patient must have undergone breast +/- axillary surgery with curative intent for the current malignancy =8 weeks before randomization. The final primary tumor surgical specimen must have R0 margins free from tumor. - Patients must have sufficient resolution of any surgical side effects from the last surgery per physician assessment, with no active wound healing complications at the time of randomization. - Incentive to undergo adjuvant radiation therapy when indicated per local institutional guidelines. Note: For patients in the palbociclib arm, radiation therapy when indicated has to start =9 weeks after last surgery. The endocrine therapy can be initiated during or after the radiation therapy but not later than 3 weeks after the last radiotherapy. Palbociclib has to start =3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine therapy and palbociclib have to be initiated =9 weeks after last surgery. Note: For patients in the chemotherapy arm, chemotherapy has to be the first adjuvant treatment and has to start =9 weeks after the last surgery. When radiation therapy is indicated, this treatment has to start =6 weeks after the last chemotherapy administration. Adjuvant endocrine therapy can be initiated during or after the radiation therapy but not later than 3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine therapy has to be initiated =6 weeks after last chemotherapy administration. - Adequate baseline organ function, evidenced by the following laboratory results within 3 weeks of randomization: - Hemoglobin = 9 g/dL - Absolute neutrophil count (ANC) = 1500/mm3 - Platelet count = 100,000/mm3 - Total bilirubin = 1.5 upper limit of normal (ULN), or total bilirubin = 3.0 × ULN in patients with documented Gilbert’s Syndrome. - Glomerular Filtration Rate (GFR) = 30 ml/min according to MDRD formula or CKD-EPI formula or Cockcroft and Gault formula - SGOT (AST), SGPT (ALT) and alkaline phosphatase = 2.5 × ULN - Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption. - For men part
Exclusion criteria
Exclusion criteria: - Evidence of macroscopic distant metastases, investigated according to local institutional guidelines. - Previous history of invasive breast cancer - Systemic anticancer therapy prior to the breast cancer surgery - Prior therapy with any CDK4/6 inhibitor - Concurrent investigational agent within 28 days of randomization - Concomitant anticancer treatment with the exception of bone antiresorptive agents or LHRH agonists in male patients treated with an aromatase-inhibitor - History of allergic reactions attributed to compounds of chemical or biological composition similar to palbociclib or to chemotherapy components - Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption - Medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including known HIV, active hepatitis B and/or hepatitis C infection), symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or uncontrolled diabetes. Note: For patients for whom doxorubicin or epirubicin is planned, an adequate baseline cardiac function (left ventricular ejection fraction =50%) should have been proven no more than 1 year before treatment start. - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial - Other malignancy within the last 5 years except: adequately treated non-metastatic non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.;Secondary Objective: - To evaluate the efficacy with respect to different time-to-event endpoints (distant recurrence-free interval (DRFI), breast cancer specific survival (BCSS), OS) at 3, 6 and 10 years in both arms - To evaluate toxicity in both arms - To evaluate the treatment discontinuation and dose reduction rates in both arms - To assess the reasons for treatment discontinuation - To evaluate completion of oral therapy in the experimental arm - To assess the evolution of Health-Related Quality of Life (HRQoL) in both arms - To assess the evolution, prognostic and predictive effects of geriatric assessment in both arms ;Primary end point(s): The primary endpoint in this study is the 3-year distant recurrence-free interval rate in the experimental arm.;Timepoint(s) of evaluation of this end point: 3 years (main analysis), 6 and 10 years (long-term analyses) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Distant recurrence-free interval at 3 years in the control arm and at 6 and 10 years in both arms. - Breast cancer specific survival at 3, 6, and 10 years in both arms. - Overall survival at 3, 6 and 10 years in both arms. - Adverse events according to CTCAE v5.0 recorded at every patient visit in both arms. - Treatment discontinuation and dose reduction rates in both arms. - Reason for treatment discontinuation. - HRQoL questionnaires (modified QLQ-C30, ELD-14, and selected items from the BR45 module) at 3 months, 6 months, 1 year, 2 years, and 3 years in both arms. - Geriatric assessment tools (G8, iADL, ADL, Gait speed, CCI, social situation) at 3 months, 6 months, 1 year, 2 years, and 3 years in both arms. ;Timepoint(s) of evaluation of this end point: 3 years (main analysis), 6 and 10 years (long-term analyses) | — |
Countries
Belgium, France, Germany, Italy, Poland, Portugal, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Operations Department
European Organisation for research and treatment of Cancer
Outcome results
None listed