Pertuzumab + Trastuzumab (PH) Versus PH Plus Metronomic Chemotherapy (PHM) in the Elderly HER2+ Metastatic Breast Cancer Population Who May Continue on T-DM1 Alone Following Disease Progression While on PH / PHM: an Open-label Multicentre Randomized Phase II Selection Trial of the EORTC Elderly Task Force and Breast Cancer Group
- Female patients with histologically proven HER-2 positive
- Newly diagnosed or recurrent (after surgery) stage IV disease (TNM/AJCC v.7).
- Patients must have measurable (RECIST v. 1.1) or evaluable disease
- Performance status (PS) 0-3 (WHO)
- Age ≥ 70 years of age, or ≥ 60 years old with required number of dependencies
- Life expectancy of more than 12 weeks
- Previous adjuvant chemotherapy/anti HER-2 therapy after surgery is allowed, given
that the time interval from end of previous treatment to initiation of treatment for
metastatic disease is ≥ 6 months.
- Up to one line of anti-HER therapy (trastuzumab or lapatinib) is allowed in
combination with hormone therapy for hormone sensitive metastatic breast cancer.
- Adequate organ function
- Before patient randomization, written informed consent must be given according to
ICH/GCP, and national/local regulations.
- No brain metastases that are untreated, symptomatic, or require steroids to control
symptoms; or any radiation, surgery, or other therapy to control symptoms from brain
metastases within 2 months prior to the first study treatment.
- No prior chemotherapy for metastatic disease is allowed
- No prior treatment with pertuzumab is allowed
- No history of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin or liposomal doxorubicin > 360 mg/m2
- Epirubicin > 720 mg/m2
- Mitoxantrone > 120 mg/m2
- Idarubicin > 90 mg/m2
- If another anthracycline or more than 1 anthracycline has been used, then the
cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
- No history of palliative radiotherapy within 14 days of randomization
- No history of other malignancy within the last 5 years, except for carcinoma in situ
of the cervix or basal cell or spinocellular carcinoma of the skin
- No current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic
> 100 mmHg)
- No LVEF below 50%
- No history of significant cardiac disease defined as:
- Symptomatic CHF (NYHA classes II-IV)
- High-risk uncontrolled arrhythmias
- History of myocardial infarction within 6 months prior to randomization
- Clinically significant valvular heart disease
- No angina pectoris requiring anti-angina treatment
- No peripheral neuropathy of Grade ≥ 3 per NCI CTCAE version 4.0.
- No current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or
bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C
- No major surgical procedure or significant traumatic injury within 28 days prior to
randomization or anticipation of the need for major surgery during the course of
- No history of receiving any investigational treatment within 28 days of randomization
- No history of intolerance (including Grade 3-4 infusion reaction) to trastuzumab
- No unwillingness or inability to comply with the requirements of the protocol as
assessed by the investigator
- Absence of 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